Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Seminars in Immunopathology
Erschienen in: Seminars in Immunopathology 4/2017

17.02.2017 | Review

Selected cytokine pathways in rheumatoid arthritis

verfasst von: Mélissa Noack, Pierre Miossec

Erschienen in: Seminars in Immunopathology | Ausgabe 4/2017

Einloggen, um Zugang zu erhalten

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Cytokines play a key role in its pathogenesis. They contribute to the induction and maintenance of inflammation and thus provide therapeutic targets. Many cytokines are involved in RA, and this review focuses on a few critical ones: tumor necrosis factor (TNF), interleukin (IL)-6, IL-1, IL-17, and GM-CSF. TNF and IL-6 are both well-established targets in RA treatment, and new biologic agents are reaching the market. IL-1 represents a more complex cytokine as results in humans do not reach those in animal models. IL-17 and GM-CSF are cytokines representing new targets either as early treatment or in non-responders to other biologics. The interaction between cytokines and their signaling pathways are the basis for the development of new strategies with small molecules or bispecific antibodies. Clearly, the targeting of cytokines has been a major progress in RA treatment, but many issues remain open. Although remission can be better achieved, reactivation of the disease too often occurs upon treatment discontinuation. Better understanding and targeting of chronicity remains a goal to achieve in the future.
Literatur
1.
Aarvak T, Chabaud M, Miossec P, Natvig JB (1999) IL-17 is produced by some proinflammatory Th1/Th0 cells but not by Th2 cells. J Immunol 162:1246–1251PubMed
2.
Acosta-Rodriguez EV, Napolitani G, Lanzavecchia A, Sallusto F (2007) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8:942–949PubMedCrossRef
3.
Aggarwal BB (2003) Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3:745–756PubMedCrossRef
4.
Ajeganova S, van Steenbergen HW, van Nies JA, Burgers LE, Huizinga TW, van der Helm-van Mil AH (2015) Disease-modifying antirheumatic drug-free sustained remission in rheumatoid arthritis: an increasingly achievable outcome with subsidence of disease symptoms. Ann Rheum Dis 75:867–873PubMedCrossRef
5.
Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, Duan S, Eiwegger T, Eljaszewicz A, Ferstl R, Frei R, Garbani M, Globinska A, Hess L, Huitema C, Kubo T, Komlosi Z, Konieczna P, Kovacs N, Kucuksezer UC, Meyer N, Morita H, Olzhausen J, O’Mahony L, Pezer M, Prati M, Rebane A, Rhyner C, Rinaldi A, Sokolowska M, Stanic B, Sugita K, Treis A, van de Veen W, Wanke K, Wawrzyniak M, Wawrzyniak P, Wirz OF, Zakzuk JS, Akdis CA (2016) Interleukins (from IL-1 to IL-38), interferons, transforming growth factor beta, and TNF-alpha: Receptors, functions, and roles in diseases. J Allergy Clin Immunol 138:984–1010PubMedCrossRef
6.
Alonzi T, Fattori E, Lazzaro D, Costa P, Probert L, Kollias G, De Benedetti F, Poli V, Ciliberto G (1998) Interleukin 6 is required for the development of collagen-induced arthritis. J Exp Med 187:461–468PubMedPubMedCentralCrossRef
7.
Alten R, Gomez-Reino J, Durez P, Beaulieu A, Sebba A, Krammer G, Preiss R, Arulmani U, Widmer A, Gitton X, Kellner H (2011) Efficacy and safety of the human anti-IL-1beta monoclonal antibody canakinumab in rheumatoid arthritis: results of a 12-week, phase II, dose-finding study. BMC Musculoskelet Disord 12:153PubMedPubMedCentralCrossRef
8.
Alves JD, Marinho A, Serra MJ (2011) Tocilizumab: is there life beyond anti-TNF blockade? Int J Clin Pract 65:508–513PubMedCrossRef
9.
Apte RN, Dotan S, Elkabets M, White MR, Reich E, Carmi Y, Song X, Dvozkin T, Krelin Y, Voronov E (2006) The involvement of IL-1 in tumorigenesis, tumor invasiveness, metastasis and tumor-host interactions. Cancer Metastasis Rev 25:387–408PubMedCrossRef
10.
Arend WP (2001) Cytokine imbalance in the pathogenesis of rheumatoid arthritis: the role of interleukin-1 receptor antagonist. Semin Arthritis Rheum 30:1–6PubMedCrossRef
11.
Arner EC, Harris RR, DiMeo TM, Collins RC, Galbraith W (1995) Interleukin-1 receptor antagonist inhibits proteoglycan breakdown in antigen induced but not polycation induced arthritis in the rabbit. J Rheumatol 22:1338–1346PubMed
12.
Asquith DL, Miller AM, McInnes IB, Liew FY (2009) Animal models of rheumatoid arthritis. Eur J Immunol 39:2040–2044PubMedCrossRef
13.
Atzeni F, Talotta R, Salaffi F, Cassinotti A, Varisco V, Battellino M, Ardizzone S, Pace F, Sarzi-Puttini P (2013) Immunogenicity and autoimmunity during anti-TNF therapy. Autoimmun Rev 12:703–708PubMedCrossRef
14.
15.
Behrens F, Tak PP, Ostergaard M, Stoilov R, Wiland P, Huizinga TW, Berenfus VY, Vladeva S, Rech J, Rubbert-Roth A, Korkosz M, Rekalov D, Zupanets IA, Ejbjerg BJ, Geiseler J, Fresenius J, Korolkiewicz RP, Schottelius AJ, Burkhardt H (2014) MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis 74:1058–1064PubMedPubMedCentralCrossRef
16.
Bell AL, Magill MK, McKane WR, Kirk F, Irvine AE (1995) Measurement of colony-stimulating factors in synovial fluid: potential clinical value. Rheumatol Int 14:177–182PubMedCrossRef
17.
Benedetti G, Miossec P (2014) Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. Eur J Immunol 44:339–347PubMedCrossRef
18.
Berenbaum F, Rajzbaum G, Amor B, Toubert A (1994) Evidence for GM-CSF receptor expression in synovial tissue. An analysis by semi-quantitative polymerase chain reaction on rheumatoid arthritis and osteoarthritis synovial biopsies. Eur Cytokine Netw 5:43–46PubMed
19.
Beringer A, Noack M, Miossec P (2016) IL-17 in chronic inflammation: from discovery to targeting. Trends Mol Med 22:230–241PubMedCrossRef
20.
Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR (1986) Stimulation of bone resorption and inhibition of bone formation in vitro by human tumour necrosis factors. Nature 319:516–518PubMedCrossRef
21.
Braumuller H, Wieder T, Brenner E, Assmann S, Hahn M, Alkhaled M, Schilbach K, Essmann F, Kneilling M, Griessinger C, Ranta F, Ullrich S, Mocikat R, Braungart K, Mehra T, Fehrenbacher B, Berdel J, Niessner H, Meier F, van den Broek M, Haring HU, Handgretinger R, Quintanilla-Martinez L, Fend F, Pesic M, Bauer J, Zender L, Schaller M, Schulze-Osthoff K, Rocken M (2013) T-helper-1-cell cytokines drive cancer into senescence. Nature 494:361–365PubMedCrossRef
22.
Brennan FM, Chantry D, Jackson A, Maini R, Feldmann M (1989) Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2:244–247PubMedCrossRef
23.
24.
Brenner D, Blaser H, Mak TW (2015) Regulation of tumour necrosis factor signalling: live or let die. Nat Rev Immunol 15:362–374PubMedCrossRef
25.
Bresnihan B (2001) The safety and efficacy of interleukin-1 receptor antagonist in the treatment of rheumatoid arthritis. Semin Arthritis Rheum 30:17–20PubMedCrossRef
26.
Bujak M, Frangogiannis NG (2009) The role of IL-1 in the pathogenesis of heart disease. Arch Immunol Ther Exp 57:165–176CrossRef
27.
28.
Burmester GR, Durez P, Shestakova G, Genovese MC, Schulze-Koops H, Li Y, Wang YA, Lewitzky S, Koroleva I, Berneis AA, Lee DM, Hueber W (2016) Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monoclonal antibody secukinumab in active rheumatoid arthritis. Rheumatology (Oxford) 55:49–55CrossRef
29.
Burmester GR, Feist E, Sleeman MA, Wang B, White B, Magrini F (2011) Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-alpha, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study. Ann Rheum Dis 70:1542–1549PubMedPubMedCentralCrossRef
30.
Burmester GR, Weinblatt ME, McInnes IB, Porter D, Barbarash O, Vatutin M, Szombati I, Esfandiari E, Sleeman MA, Kane CD, Cavet G, Wang B, Godwood A, Magrini F (2012) Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Ann Rheum Dis 72:1445–1452PubMedPubMedCentralCrossRef
31.
Butler DM, Maini RN, Feldmann M, Brennan FM (1995) Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. Comparison of monoclonal anti TNF-alpha antibody with the interleukin-1 receptor antagonist. Eur Cytokine Netw 6:225–230PubMed
32.
Bystrom J, Clanchy FI, Taher TE, Mangat P, Jawad AS, Williams RO, Mageed RA (2016) TNFalpha in the regulation of Treg and Th17 cells in rheumatoid arthritis and other autoimmune inflammatory diseases. Cytokine
33.
Callhoff J, Weiss A, Zink A, Listing J (2013) Impact of biologic therapy on functional status in patients with rheumatoid arthritis—a meta-analysis. Rheumatology (Oxford) 52:2127–2135CrossRef
34.
Campbell IK, Bendele A, Smith DA, Hamilton JA (1997) Granulocyte-macrophage colony stimulating factor exacerbates collagen induced arthritis in mice. Ann Rheum Dis 56:364–368PubMedPubMedCentralCrossRef
35.
Campbell IK, Novak U, Cebon J, Layton JE, Hamilton JA (1991) Human articular cartilage and chondrocytes produce hemopoietic colony-stimulating factors in culture in response to IL-1. J Immunol 147:1238–1246PubMed
36.
Campbell IK, Rich MJ, Bischof RJ, Dunn AR, Grail D, Hamilton JA (1998) Protection from collagen-induced arthritis in granulocyte-macrophage colony-stimulating factor-deficient mice. J Immunol 161:3639–3644PubMed
37.
Campbell IL, Erta M, Lim SL, Frausto R, May U, Rose-John S, Scheller J, Hidalgo J (2014) Trans-signaling is a dominant mechanism for the pathogenic actions of interleukin-6 in the brain. J Neurosci 34:2503–2513PubMedCrossRef
38.
Carmi Y, Dotan S, Rider P, Kaplanov I, White MR, Baron R, Abutbul S, Huszar M, Dinarello CA, Apte RN, Voronov E (2013) The role of IL-1beta in the early tumor cell-induced angiogenic response. J Immunol 190:3500–3509PubMedCrossRef
39.
Carrieri PB, Provitera V, De Rosa T, Tartaglia G, Gorga F, Perrella O (1998) Profile of cerebrospinal fluid and serum cytokines in patients with relapsing-remitting multiple sclerosis: a correlation with clinical activity. Immunopharmacol Immunotoxicol 20:373–382PubMedCrossRef
40.
Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L, Miossec P (1999) Human interleukin-17: A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 42:963–970PubMedCrossRef
41.
Chabaud M, Fossiez F, Taupin JL, Miossec P (1998) Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol 161:409–414PubMed
42.
Chabaud M, Garnero P, Dayer JM, Guerne PA, Fossiez F, Miossec P (2000) Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis. Cytokine 12:1092–1099PubMedCrossRef
43.
Chabaud M, Lubberts E, Joosten L, van Den Berg W, Miossec P (2001) IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res 3:168–177PubMedPubMedCentralCrossRef
44.
Chabaud M, Miossec P (2001) The combination of tumor necrosis factor alpha blockade with interleukin-1 and interleukin-17 blockade is more effective for controlling synovial inflammation and bone resorption in an ex vivo model. Arthritis Rheum 44:1293–1303PubMedCrossRef
45.
Chabaud M, Page G, Miossec P (2001) Enhancing effect of IL-1, IL-17, and TNF-alpha on macrophage inflammatory protein-3alpha production in rheumatoid arthritis: regulation by soluble receptors and Th2 cytokines. J Immunol 167:6015–6020PubMedCrossRef
46.
Chandrasekhar S, Harvey AK, Hrubey PS, Bendele AM (1990) Arthritis induced by interleukin-1 is dependent on the site and frequency of intraarticular injection. Clin Immunol Immunopathol 55:382–400PubMedCrossRef
47.
Chen CJ, Kono H, Golenbock D, Reed G, Akira S, Rock KL (2007) Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med 13:851–856PubMedCrossRef
48.
Chou DB, Sworder B, Bouladoux N, Roy CN, Uchida AM, Grigg M, Robey PG, Belkaid Y (2012) Stromal-derived IL-6 alters the balance of myeloerythroid progenitors during Toxoplasma gondii infection. J Leukoc Biol 92:123–131PubMedPubMedCentralCrossRef
49.
Choy EH, Isenberg DA, Garrood T, Farrow S, Ioannou Y, Bird H, Cheung N, Williams B, Hazleman B, Price R, Yoshizaki K, Nishimoto N, Kishimoto T, Panayi GS (2002) Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial. Arthritis Rheum 46:3143–3150PubMedCrossRef
50.
Choy EH, Kavanaugh AF, Jones SA (2013) The problem of choice: current biologic agents and future prospects in RA. Nat Rev Rheumatol 9:154–163PubMedCrossRef
51.
Cohen I, Rider P, Carmi Y, Braiman A, Dotan S, White MR, Voronov E, Martin MU, Dinarello CA, Apte RN (2010) Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc Natl Acad Sci U S A 107:2574–2579PubMedPubMedCentralCrossRef
52.
Cohen S, Hurd E, Cush J, Schiff M, Weinblatt ME, Moreland LW, Kremer J, Bear MB, Rich WJ, McCabe D (2002) Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46:614–624PubMedCrossRef
53.
Cook AD, Braine EL, Campbell IK, Rich MJ, Hamilton JA (2001) Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease. Arthritis Res 3:293–298PubMedPubMedCentralCrossRef
54.
Cook AD, Braine EL, Hamilton JA (2004) Stimulus-dependent requirement for granulocyte-macrophage colony-stimulating factor in inflammation. J Immunol 173:4643–4651PubMedCrossRef
55.
Cook AD, Pobjoy J, Sarros S, Steidl S, Durr M, Lacey DC, Hamilton JA (2013) Granulocyte-macrophage colony-stimulating factor is a key mediator in inflammatory and arthritic pain. Ann Rheum Dis 72:265–270PubMedCrossRef
56.
Cook AD, Pobjoy J, Steidl S, Durr M, Braine EL, Turner AL, Lacey DC, Hamilton JA (2012) Granulocyte-macrophage colony-stimulating factor is a key mediator in experimental osteoarthritis pain and disease development. Arthritis Res Ther 14:R199PubMedPubMedCentralCrossRef
57.
Cowburn AS, Summers C, Dunmore BJ, Farahi N, Hayhoe RP, Print CG, Cook SJ, Chilvers ER (2011) Granulocyte/macrophage colony-stimulating factor causes a paradoxical increase in the BH3-only pro-apoptotic protein Bim in human neutrophils. Am J Respir Cell Mol Biol 44:879–887PubMedCrossRef
58.
Dayer JM, Bresnihan B (2002) Targeting interleukin-1 in the treatment of rheumatoid arthritis. Arthritis Rheum 46:574–578PubMedCrossRef
59.
Dayer JM, de Rochemonteix B, Burrus B, Demczuk S, Dinarello CA (1986) Human recombinant interleukin 1 stimulates collagenase and prostaglandin E2 production by human synovial cells. J Clin Invest 77:645–648PubMedPubMedCentralCrossRef
60.
de Vries EG, Willemse PH, Biesma B, Stern AC, Limburg PC, Vellenga E (1991) Flare-up of rheumatoid arthritis during GM-CSF treatment after chemotherapy. Lancet 338:517–518PubMedCrossRef
61.
de Vries N, Tak PP (2005) The response to anti-TNF-alpha treatment: gene regulation at the bedside. Rheumatology (Oxford) 44:705–707CrossRef
62.
Dennis G Jr, Holweg CT, Kummerfeld SK, Choy DF, Setiadi AF, Hackney JA, Haverty PM, Gilbert H, Lin WY, Diehl L, Fischer S, Song A, Musselman D, Klearman M, Gabay C, Kavanaugh A, Endres J, Fox DA, Martin F, Townsend MJ (2014) Synovial phenotypes in rheumatoid arthritis correlate with response to biologic therapeutics. Arthritis Res Ther 16:R90PubMedPubMedCentralCrossRef
63.
64.
Dinarello CA, Renfer L, Wolff SM (1977) Human leukocytic pyrogen: purification and development of a radioimmunoassay. Proc Natl Acad Sci U S A 74:4624–4627PubMedPubMedCentralCrossRef
65.
Drevlow BE, Lovis R, Haag MA, Sinacore JM, Jacobs C, Blosche C, Landay A, Moreland LW, Pope RM (1996) Recombinant human interleukin-1 receptor type I in the treatment of patients with active rheumatoid arthritis. Arthritis Rheum 39:257–265PubMedCrossRef
66.
Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA (2013) Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 13:759–771PubMedCrossRef
67.
Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, Leeb B, Breedveld FC, Macfarlane JD, Bijl H et al (1994) Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 344:1105–1110PubMedCrossRef
68.
Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Katsikis P, Brennan FM, Walker J, Bijl H, Ghrayeb J et al (1993) Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 36:1681–1690PubMedCrossRef
69.
Farahat MN, Yanni G, Poston R, Panayi GS (1993) Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Ann Rheum Dis 52:870–875PubMedPubMedCentralCrossRef
70.
71.
Feige U, Karbowski A, Rordorf-Adam C, Pataki A (1989) Arthritis induced by continuous infusion of hr-interleukin-1 alpha into the rabbit knee-joint. Int J Tissue React 11:225–238PubMed
72.
Feldmann M (2009) Translating molecular insights in autoimmunity into effective therapy. Annu Rev Immunol 27:1–27PubMedCrossRef
73.
74.
Feldmann M, Brennan FM, Maini RN (1996) Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14:397–440PubMedCrossRef
75.
Fiehn C, Wermann M, Pezzutto A, Hufner M, Heilig B (1992) Plasma GM-CSF concentrations in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropathy. Z Rheumatol 51:121–126PubMed
76.
Field M, Clinton L (1993) Expression of GM-CSF receptor in rheumatoid arthritis. Lancet 342:1244PubMedCrossRef
77.
78.
Fleetwood AJ, Cook AD, Hamilton JA (2005) Functions of granulocyte-macrophage colony-stimulating factor. Crit Rev Immunol 25:405–428PubMedCrossRef
79.
Fleetwood AJ, Dinh H, Cook AD, Hertzog PJ, Hamilton JA (2009) GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on type I interferon signaling. J Leukoc Biol 86:411–421PubMedCrossRef
80.
Fleetwood AJ, Lawrence T, Hamilton JA, Cook AD (2007) Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation. J Immunol 178:5245–5252PubMedCrossRef
81.
Fleischmann R, van Adelsberg J, Lin Y, da Rocha Castelar-Pinheiro G, Brzezicki J, Hrycaj P, Graham NM, van Hoogstraten H, Bauer D, Burmester GR (2016) Sarilumab and non-biologic disease-modifying antirheumatic drugs in patients with active RA and inadequate response or intolerance to TNF inhibitors. Arthritis Rheumatol
82.
Fonseca JE, Carvalho T, Cruz M, Nero P, Sobral M, Mourao AF, Cavaleiro J, Ligeiro D, Abreu I, Carmo-Fonseca M, Branco JC (2005) Polymorphism at position −308 of the tumour necrosis factor alpha gene and rheumatoid arthritis pharmacogenetics. Ann Rheum Dis 64:793–794PubMedPubMedCentralCrossRef
83.
Fossiez F, Djossou O, Chomarat P, Flores-Romo L, Ait-Yahia S, Maat C, Pin JJ, Garrone P, Garcia E, Saeland S, Blanchard D, Gaillard C, Das Mahapatra B, Rouvier E, Golstein P, Banchereau J, Lebecque S (1996) T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 183:2593–2603PubMedCrossRef
84.
Fujimoto M, Serada S, Mihara M, Uchiyama Y, Yoshida H, Koike N, Ohsugi Y, Nishikawa T, Ripley B, Kimura A, Kishimoto T, Naka T (2008) Interleukin-6 blockade suppresses autoimmune arthritis in mice by the inhibition of inflammatory Th17 responses. Arthritis Rheum 58:3710–3719PubMedCrossRef
85.
Gabay C, Lamacchia C, Palmer G (2010) IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol 6:232–241PubMedCrossRef
86.
Gabay C, Marinova-Mutafchieva L, Williams RO, Gigley JP, Butler DM, Feldmann M, Arend WP (2001) Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: a possible role in the resolution of arthritis. Arthritis Rheum 44:451–462PubMedCrossRef
87.
88.
89.
90.
91.
Geiler J, McDermott MF (2010) Gevokizumab, an anti-IL-1beta mAb for the potential treatment of type 1 and 2 diabetes, rheumatoid arthritis and cardiovascular disease. Curr Opin Mol Ther 12:755–769PubMed
92.
Genovese MC, Cohen S, Moreland L, Lium D, Robbins S, Newmark R, Bekker P (2004) Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis Rheum 50:1412–1419PubMedCrossRef
93.
Genovese MC, Durez P, Richards HB, Supronik J, Dokoupilova E, Aelion JA, Lee SH, Codding CE, Kellner H, Ikawa T, Hugot S, Ligozio G, Mpofu S (2014) One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis: phase II, dose-finding, double-blind, randomized, placebo-controlled study. J Rheumatol 41:414–421PubMedCrossRef
94.
Genovese MC, Durez P, Richards HB, Supronik J, Dokoupilova E, Mazurov V, Aelion JA, Lee SH, Codding CE, Kellner H, Ikawa T, Hugot S, Mpofu S (2013) Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis 72:863–869PubMedCrossRef
95.
Genovese MC, Fleischmann R, Furst D, Janssen N, Carter J, Dasgupta B, Bryson J, Duncan B, Zhu W, Pitzalis C, Durez P, Kretsos K (2014) Efficacy and safety of olokizumab in patients with rheumatoid arthritis with an inadequate response to TNF inhibitor therapy: outcomes of a randomised phase IIb study. Ann Rheum Dis 73:1607–1615PubMedPubMedCentralCrossRef
96.
Genovese MC, Fleischmann R, Kivitz AJ, Rell-Bakalarska M, Martincova R, Fiore S, Rohane P, van Hoogstraten H, Garg A, Fan C, van Adelsberg J, Weinstein SP, Graham NM, Stahl N, Yancopoulos GD, Huizinga TW, van der Heijde D (2015) Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a phase III Study. Arthritis Rheumatol 67:1424–1437PubMedCrossRef
97.
Genovese MC, Greenwald M, Cho CS, Berman A, Jin L, Cameron GS, Benichou O, Xie L, Braun D, Berclaz PY, Banerjee S (2014) A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors. Arthritis Rheumatol 66:1693–1704PubMedCrossRef
98.
Ghivizzani SC, Kang R, Georgescu HI, Lechman ER, Jaffurs D, Engle JM, Watkins SC, Tindal MH, Suchanek MK, McKenzie LR, Evans CH, Robbins PD (1997) Constitutive intra-articular expression of human IL-1 beta following gene transfer to rabbit synovium produces all major pathologies of human rheumatoid arthritis. J Immunol 159:3604–3612PubMed
99.
Ghivizzani SC, Lechman ER, Tio C, Mule KM, Chada S, McCormack JE, Evans CH, Robbins PD (1997) Direct retrovirus-mediated gene transfer to the synovium of the rabbit knee: implications for arthritis gene therapy. Gene Ther 4:977–982PubMedCrossRef
100.
Hamilton JA (2008) Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 8:533–544PubMedCrossRef
101.
Hansen G, Hercus TR, McClure BJ, Stomski FC, Dottore M, Powell J, Ramshaw H, Woodcock JM, Xu Y, Guthridge M, McKinstry WJ, Lopez AF, Parker MW (2008) The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell 134:496–507PubMedCrossRef
102.
Hashizume M, Hayakawa N, Mihara M (2008) IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-alpha and IL-17. Rheumatology (Oxford) 47:1635–1640CrossRef
103.
104.
Haudek SB, Taffet GE, Schneider MD, Mann DL (2007) TNF provokes cardiomyocyte apoptosis and cardiac remodeling through activation of multiple cell death pathways. J Clin Invest 117:2692–2701PubMedPubMedCentralCrossRef
105.
Haworth C, Brennan FM, Chantry D, Turner M, Maini RN, Feldmann M (1991) Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur J Immunol 21:2575–2579PubMedCrossRef
106.
Hazenberg BP, Van Leeuwen MA, Van Rijswijk MH, Stern AC, Vellenga E (1989) Correction of granulocytopenia in Felty’s syndrome by granulocyte-macrophage colony-stimulating factor. Simultaneous induction of interleukin-6 release and flare-up of the arthritis. Blood 74:2769–2770PubMed
107.
Henderson B, Pettipher ER (1988) Comparison of the in vivo inflammatory activities after intra-articular injection of natural and recombinant IL-1 alpha and IL-1 beta in the rabbit. Biochem Pharmacol 37:4171–4176PubMedCrossRef
108.
Hercus TR, Dhagat U, Kan WL, Broughton SE, Nero TL, Perugini M, Sandow JJ, D’Andrea RJ, Ekert PG, Hughes T, Parker MW, Lopez AF (2013) Signalling by the betac family of cytokines. Cytokine Growth Factor Rev 24:189–201PubMedCrossRef
109.
Hercus TR, Thomas D, Guthridge MA, Ekert PG, King-Scott J, Parker MW, Lopez AF (2009) The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood 114:1289–1298PubMedPubMedCentralCrossRef
110.
Hess A, Axmann R, Rech J, Finzel S, Heindl C, Kreitz S, Sergeeva M, Saake M, Garcia M, Kollias G, Straub RH, Sporns O, Doerfler A, Brune K, Schett G (2011) Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A 108:3731–3736PubMedPubMedCentralCrossRef
111.
Hetland ML, Christensen IJ, Tarp U, Dreyer L, Hansen A, Hansen IT, Kollerup G, Linde L, Lindegaard HM, Poulsen UE, Schlemmer A, Jensen DV, Jensen S, Hostenkamp G, Ostergaard M (2010) Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry. Arthritis Rheum 62:22–32PubMedCrossRef
112.
Hirano T, Matsuda T, Turner M, Miyasaka N, Buchan G, Tang B, Sato K, Shimizu M, Maini R, Feldmann M et al (1988) Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol 18:1797–1801PubMedCrossRef
113.
Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, Iwakura Y, Sakaguchi N, Sakaguchi S (2007) T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med 204:41–47PubMedPubMedCentralCrossRef
114.
Hoge J, Yan I, Janner N, Schumacher V, Chalaris A, Steinmetz OM, Engel DR, Scheller J, Rose-John S, Mittrucker HW (2013) IL-6 controls the innate immune response against Listeria monocytogenes via classical IL-6 signaling. J Immunol 190:703–711PubMedCrossRef
115.
Honorati MC, Neri S, Cattini L, Facchini A (2006) Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts. Osteoarthr Cartil 14:345–352PubMedCrossRef
116.
Horai R, Saijo S, Tanioka H, Nakae S, Sudo K, Okahara A, Ikuse T, Asano M, Iwakura Y (2000) Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J Exp Med 191:313–320PubMedPubMedCentralCrossRef
117.
Hot A, Zrioual S, Lenief V, Miossec P (2012) IL-17 and tumour necrosis factor alpha combination induces a HIF-1alpha-dependent invasive phenotype in synoviocytes. Ann Rheum Dis 71:1393–1401PubMedCrossRef
118.
Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH, Durez P, Tak PP, Gomez-Reino JJ, Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD, Rose K, Haider A, Di Padova F (2010) Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2:52ra72
119.
Huizinga TW, Fleischmann RM, Jasson M, Radin AR, van Adelsberg J, Fiore S, Huang X, Yancopoulos GD, Stahl N, Genovese MC (2014) Sarilumab, a fully human monoclonal antibody against IL-6Ralpha in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis 73:1626–1634PubMedCrossRef
120.
Hunter CA, Jones SA (2015) IL-6 as a keystone cytokine in health and disease. Nat Immunol 16:448–457PubMedCrossRef
121.
Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y, Fujikado N, Tanahashi Y, Akitsu A, Kotaki H, Sudo K, Nakae S, Sasakawa C, Iwakura Y (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30:108–119PubMedCrossRef
122.
Isomaki P, Junttila I, Vidqvist KL, Korpela M, Silvennoinen O (2015) The activity of JAK-STAT pathways in rheumatoid arthritis: constitutive activation of STAT3 correlates with interleukin 6 levels. Rheumatology (Oxford) 54:1103–1113CrossRef
123.
Iwakura Y, Ishigame H, Saijo S, Nakae S (2011) Functional specialization of interleukin-17 family members. Immunity 34:149–162PubMedCrossRef
124.
Jacques C, Gosset M, Berenbaum F, Gabay C (2006) The role of IL-1 and IL-1Ra in joint inflammation and cartilage degradation. Vitam Horm 74:371–403PubMedCrossRef
125.
Jones GW, McLoughlin RM, Hammond VJ, Parker CR, Williams JD, Malhotra R, Scheller J, Williams AS, Rose-John S, Topley N, Jones SA (2010) Loss of CD4+ T cell IL-6R expression during inflammation underlines a role for IL-6 trans signaling in the local maintenance of Th17 cells. J Immunol 184:2130–2139PubMedCrossRef
126.
Jones SA (2005) Directing transition from innate to acquired immunity: defining a role for IL-6. J Immunol 175:3463–3468PubMedCrossRef
127.
128.
Joosten LA, Helsen MM, Saxne T, van De Loo FA, Heinegard D, van Den Berg WB (1999) IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation. J Immunol 163:5049–5055PubMed
129.
Jostock T, Mullberg J, Ozbek S, Atreya R, Blinn G, Voltz N, Fischer M, Neurath MF, Rose-John S (2001) Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem 268:160–167PubMedCrossRef
130.
Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B (1990) Constitutive production of interleukin-6 and immunologic features in cardiac myxomas. Arthritis Rheum 33:398–402PubMedCrossRef
131.
Jouvenne P, Fossiez F, Banchereau J, Miossec P (1997) High levels of neutralizing autoantibodies against IL-1 alpha are associated with a better prognosis in chronic polyarthritis: a follow-up study. Scand J Immunol 46:413–418PubMedCrossRef
132.
Kalliolias GD, Ivashkiv LB (2016) TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol 12:49–62PubMedCrossRef
133.
Katchamart W, Johnson S, Lin HJ, Phumethum V, Salliot C, Bombardier C (2010) Predictors for remission in rheumatoid arthritis patients: a systematic review. Arthritis Care Res (Hoboken) 62:1128–1143CrossRef
134.
Keffer J, Probert L, Cazlaris H, Georgopoulos S, Kaslaris E, Kioussis D, Kollias G (1991) Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 10:4025–4031PubMedPubMedCentral
135.
Kievit W, Adang EM, Fransen J, Kuper HH, van de Laar MA, Jansen TL, De Gendt CM, De Rooij DJ, Brus HL, Van Oijen PC, Van Riel PC (2008) The effectiveness and medication costs of three anti-tumour necrosis factor alpha agents in the treatment of rheumatoid arthritis from prospective clinical practice data. Ann Rheum Dis 67:1229–1234PubMedCrossRef
136.
King IL, Dickendesher TL, Segal BM (2009) Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. Blood 113:3190–3197PubMedPubMedCentralCrossRef
137.
Kirkham BW, Lassere MN, Edmonds JP, Juhasz KM, Bird PA, Lee CS, Shnier R, Portek IJ (2006) Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort). Arthritis Rheum 54:1122–1131PubMedCrossRef
138.
Koenders MI, Lubberts E, Oppers-Walgreen B, van den Bersselaar L, Helsen MM, Di Padova FE, Boots AM, Gram H, Joosten LA, van den Berg WB (2005) Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1. Am J Pathol 167:141–149PubMedPubMedCentralCrossRef
139.
Koenders MI, van den Berg WB (2016) Secukinumab for rheumatology: development and its potential place in therapy. Drug Des Devel Ther 10:2069–2080PubMedPubMedCentralCrossRef
140.
Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476PubMedCrossRef
141.
Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, Zinkernagel R, Bluethmann H, Kohler G (1994) Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368:339–342PubMedCrossRef
142.
Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL (2000) TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 106:1481–1488PubMedPubMedCentralCrossRef
143.
Lawlor KE, Wong PK, Campbell IK, van Rooijen N, Wicks IP (2005) Acute CD4+ T lymphocyte-dependent interleukin-1-driven arthritis selectively requires interleukin-2 and interleukin-4, joint macrophages, granulocyte-macrophage colony-stimulating factor, interleukin-6, and leukemia inhibitory factor. Arthritis Rheum 52:3749–3754PubMedCrossRef
144.
Lazzerini PE, Capecchi PL, Guidelli GM, Selvi E, Acampa M, Laghi-Pasini F (2016) Spotlight on sirukumab for the treatment of rheumatoid arthritis: the evidence to date. Drug Des Devel Ther 10:3083–3098PubMedPubMedCentralCrossRef
145.
Lee A, Qiao Y, Grigoriev G, Chen J, Park-Min KH, Park SH, Ivashkiv LB, Kalliolias GD (2013) Tumor necrosis factor alpha induces sustained signaling and a prolonged and unremitting inflammatory response in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 65:928–938PubMedPubMedCentralCrossRef
146.
Leizer T, Cebon J, Layton JE, Hamilton JA (1990) Cytokine regulation of colony-stimulating factor production in cultured human synovial fibroblasts: I. Induction of GM-CSF and G-CSF production by interleukin-1 and tumor necrosis factor. Blood 76:1989–1996PubMed
147.
Liontos LM, Dissanayake D, Ohashi PS, Weiss A, Dragone LL, McGlade CJ (2011) The Src-like adaptor protein regulates GM-CSFR signaling and monocytic dendritic cell maturation. J Immunol 186:1923–1933PubMedCrossRef
148.
Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, Stoyanova-Scholz M, Gromnica-Ihle E, Antoni C, Herzer P, Kekow J, Schneider M, Zink A (2005) Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum 52:3403–3412PubMedCrossRef
149.
Liu B, Tan W, Barsoum A, Gu X, Chen K, Huang W, Ramsay A, Kolls JK, Schwarzenberger P (2010) IL-17 is a potent synergistic factor with GM-CSF in mice in stimulating myelopoiesis, dendritic cell expansion, proliferation, and functional enhancement. Exp Hematol 38(877–884):e871
150.
Liu C, Qian W, Qian Y, Giltiay NV, Lu Y, Swaidani S, Misra S, Deng L, Chen ZJ, Li X (2009) Act1, a U-box E3 ubiquitin ligase for IL-17 signaling. Sci Signal 2:ra63
151.
Liu F, Poursine-Laurent J, Wu HY, Link DC (1997) Interleukin-6 and the granulocyte colony-stimulating factor receptor are major independent regulators of granulopoiesis in vivo but are not required for lineage commitment or terminal differentiation. Blood 90:2583–2590PubMed
152.
Locksley RM, Killeen N, Lenardo MJ (2001) The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104:487–501PubMedCrossRef
153.
Lopetuso LR, Chowdhry S, Pizarro TT (2013) Opposing functions of classic and novel IL-1 family members in gut health and disease. Front Immunol 4:181PubMedPubMedCentralCrossRef
154.
Lubberts E, Joosten LA, van de Loo FA, Schwarzenberger P, Kolls J, van den Berg WB (2002) Overexpression of IL-17 in the knee joint of collagen type II immunized mice promotes collagen arthritis and aggravates joint destruction. Inflamm Res 51:102–104PubMedCrossRef
155.
Lubberts E, Koenders MI, Oppers-Walgreen B, van den Bersselaar L, Coenen-de Roo CJ, Joosten LA, van den Berg WB (2004) Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthritis Rheum 50:650–659PubMedCrossRef
156.
Lubberts E, Schwarzenberger P, Huang W, Schurr JR, Peschon JJ, van den Berg WB, Kolls JK (2005) Requirement of IL-17 receptor signaling in radiation-resistant cells in the joint for full progression of destructive synovitis. J Immunol 175:3360–3368PubMedCrossRef
157.
Ma Y, Thornton S, Boivin GP, Hirsh D, Hirsch R, Hirsch E (1998) Altered susceptibility to collagen-induced arthritis in transgenic mice with aberrant expression of interleukin-1 receptor antagonist. Arthritis Rheum 41:1798–1805PubMedCrossRef
158.
Madhok R, Crilly A, Watson J, Capell HA (1993) Serum interleukin 6 levels in rheumatoid arthritis: correlations with clinical and laboratory indices of disease activity. Ann Rheum Dis 52:232–234PubMedPubMedCentralCrossRef
159.
160.
Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555PubMedCrossRef
161.
Martin DA, Churchill M, Flores-Suarez L, Cardiel MH, Wallace D, Martin R, Phillips K, Kaine JL, Dong H, Salinger D, Stevens E, Russell CB, Chung JB (2013) A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis. Arthritis Res Ther 15:R164PubMedPubMedCentralCrossRef
162.
McDermott MF (2009) Rilonacept in the treatment of chronic inflammatory disorders. Drugs Today (Barc) 45:423–430CrossRef
163.
McInnes IB, Buckley CD, Isaacs JD (2016) Cytokines in rheumatoid arthritis—shaping the immunological landscape. Nat Rev Rheumatol 12:63–68PubMedCrossRef
164.
McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442PubMedCrossRef
165.
Md Yusof MY, Emery P (2013) Targeting interleukin-6 in rheumatoid arthritis. Drugs 73:341–356PubMedCrossRef
166.
Mease P, Strand V, Shalamberidze L, Dimic A, Raskina T, Xu LA, Liu Y, Smith J (2012) A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate. Ann Rheum Dis 71:1183–1189PubMedCrossRef
167.
Mertens M, Singh JA (2009) Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol 36:1118–1125PubMedCrossRef
168.
Metawi SA, Abbas D, Kamal MM, Ibrahim MK (2011) Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA. Clin Rheumatol 30:1201–1207PubMedCrossRef
169.
170.
171.
Mihara M, Moriya Y, Kishimoto T, Ohsugi Y (1995) Interleukin-6 (IL-6) induces the proliferation of synovial fibroblastic cells in the presence of soluble IL-6 receptor. Br J Rheumatol 34:321–325PubMedCrossRef
172.
Miller EA, Ernst JD (2008) Illuminating the black box of TNF action in tuberculous granulomas. Immunity 29:175–177PubMedCrossRef
173.
174.
Miossec P (2003) Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy. Arthritis Rheum 48:594–601PubMedCrossRef
175.
Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11:763–776PubMedCrossRef
176.
Miossec P, Korn T, Kuchroo VK (2009) Interleukin-17 and type 17 helper T cells. N Engl J Med 361:888–898PubMedCrossRef
177.
Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, Ettlinger RE, Cohen S, Koopman WJ, Mohler K, Widmer MB, Blosch CM (1997) Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 337:141–147PubMedCrossRef
178.
Nadkarni S, Mauri C, Ehrenstein MR (2007) Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J Exp Med 204:33–39PubMedPubMedCentralCrossRef
179.
Nagy G, van Vollenhoven RF (2015) Sustained biologic-free and drug-free remission in rheumatoid arthritis, where are we now? Arthritis Res Ther 17:181PubMedPubMedCentralCrossRef
180.
Nakae S, Nambu A, Sudo K, Iwakura Y (2003) Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol 171:6173–6177PubMedCrossRef
181.
Narazaki M, Yasukawa K, Saito T, Ohsugi Y, Fukui H, Koishihara Y, Yancopoulos GD, Taga T, Kishimoto T (1993) Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130. Blood 82:1120–1126PubMed
182.
Ndongo-Thiam N, Clement A, Pin JJ, Razanajaona-Doll D, Miossec P (2016) Negative association between autoantibodies against IL-17, IL-17/anti-IL-17 antibody immune complexes and destruction in rheumatoid arthritis. Ann Rheum Dis 75:1420–1422PubMedCrossRef
183.
Ndongo-Thiam N, Miossec P (2015) A cell-based bioassay for circulating bioactive IL-17: application to destruction in rheumatoid arthritis. Ann Rheum Dis 74:1629–1631PubMedCrossRef
184.
Netea MG, Simon A, van de Veerdonk F, Kullberg BJ, Van der Meer JW, Joosten LA (2010) IL-1beta processing in host defense: beyond the inflammasomes. PLoS Pathog 6:e1000661PubMedPubMedCentralCrossRef
185.
Neveu WA, Allard JB, Dienz O, Wargo MJ, Ciliberto G, Whittaker LA, Rincon M (2009) IL-6 is required for airway mucus production induced by inhaled fungal allergens. J Immunol 183:1732–1738PubMedPubMedCentralCrossRef
186.
Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Murata N, van der Heijde D, Kishimoto T (2007) Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an X ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 66:1162–1167PubMedPubMedCentralCrossRef
187.
Nishimoto N, Yoshizaki K, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Hashimoto J, Azuma J, Kishimoto T (2004) Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 50:1761–1769PubMedCrossRef
188.
Noack M, Ndongo-Thiam N, Miossec P (2016) Interaction among activated lymphocytes and mesenchymal cells through podoplanin is critical for a high IL-17 secretion. Arthritis Res Ther 18:148PubMedPubMedCentralCrossRef
189.
Novatchkova M, Leibbrandt A, Werzowa J, Neubuser A, Eisenhaber F (2003) The STIR-domain superfamily in signal transduction, development and immunity. Trends Biochem Sci 28:226–229PubMedCrossRef
190.
O’Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A (2015) The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med 66:311–328PubMedCrossRef
191.
Ohshima S, Saeki Y, Mima T, Sasai M, Nishioka K, Nomura S, Kopf M, Katada Y, Tanaka T, Suemura M, Kishimoto T (1998) Interleukin 6 plays a key role in the development of antigen-induced arthritis. Proc Natl Acad Sci U S A 95:8222–8226PubMedPubMedCentralCrossRef
192.
Osta B, Benedetti G, Miossec P (2014) Classical and paradoxical effects of TNF-alpha on bone homeostasis. Front Immunol 5:48PubMedPubMedCentral
193.
Osta B, Lavocat F, Eljaafari A, Miossec P (2014) Effects of interleukin-17A on osteogenic differentiation of isolated human mesenchymal stem cells. Front Immunol 5:425PubMedPubMedCentral
194.
195.
Pavelka K, Chon Y, Newmark R, Lin SL, Baumgartner S, Erondu N (2015) A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate. J Rheumatol 42:912–919PubMedCrossRef
196.
Pereira J, Velloso ED, Loterio HA, Laurindo IM, Chamone DA (1994) Long-term remission of neutropenia in Felty’s syndrome after a short GM-CSF treatment. Acta Haematol 92:154–156PubMedCrossRef
197.
Peters M, Jacobs S, Ehlers M, Vollmer P, Mullberg J, Wolf E, Brem G, KH M z B, Rose-John S (1996) The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6. J Exp Med 183:1399–1406PubMedCrossRef
198.
Pettipher ER, Higgs GA, Henderson B (1986) Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci U S A 83:8749–8753PubMedPubMedCentralCrossRef
199.
Plater-Zyberk C, Joosten LA, Helsen MM, Hepp J, Baeuerle PA, van den Berg WB (2007) GM-CSF neutralisation suppresses inflammation and protects cartilage in acute streptococcal cell wall arthritis of mice. Ann Rheum Dis 66:452–457PubMedCrossRef
200.
Plater-Zyberk C, Joosten LA, Helsen MM, Koenders MI, Baeuerle PA, van den Berg WB (2009) Combined blockade of granulocyte-macrophage colony stimulating factor and interleukin 17 pathways potently suppresses chronic destructive arthritis in a tumour necrosis factor alpha-independent mouse model. Ann Rheum Dis 68:721–728PubMedCrossRef
201.
Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN (2007) GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol 178:39–48PubMedCrossRef
202.
Probert L (2015) TNF and its receptors in the CNS: The essential, the desirable and the deleterious effects. Neuroscience 302:2–22PubMedCrossRef
203.
Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-Wit D, Xiao J, Lu Y, Giltiay N, Liu J, Kordula T, Zhang QW, Vallance B, Swaidani S, Aronica M, Tuohy VK, Hamilton T, Li X (2007) The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol 8:247–256PubMedCrossRef
204.
Ramiro S, Gaujoux-Viala C, Nam JL, Smolen JS, Buch M, Gossec L, van der Heijde D, Winthrop K, Landewe R (2014) Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 73:529–535PubMedCrossRef
205.
206.
Sack U, Kinne RW, Marx T, Heppt P, Bender S, Emmrich F (1993) Interleukin-6 in synovial fluid is closely associated with chronic synovitis in rheumatoid arthritis. Rheumatol Int 13:45–51PubMedCrossRef
207.
Schett G, Dayer JM, Manger B (2015) Interleukin-1 function and role in rheumatic disease. Nat Rev Rheumatol 12:14–24PubMedCrossRef
208.
Schett G, Elewaut D, McInnes IB, Dayer JM, Neurath MF (2013) How cytokine networks fuel inflammation: toward a cytokine-based disease taxonomy. Nat Med 19:822–824PubMedCrossRef
209.
Schweizerhof M, Stosser S, Kurejova M, Njoo C, Gangadharan V, Agarwal N, Schmelz M, Bali KK, Michalski CW, Brugger S, Dickenson A, Simone DA, Kuner R (2009) Hematopoietic colony-stimulating factors mediate tumor-nerve interactions and bone cancer pain. Nat Med 15:802–807PubMedCrossRef
210.
Sesin CA, Bingham CO 3rd (2005) Remission in rheumatoid arthritis: wishful thinking or clinical reality? Semin Arthritis Rheum 35:185–196PubMedCrossRef
211.
Shetty A, Hanson R, Korsten P, Shawagfeh M, Arami S, Volkov S, Vila O, Swedler W, Shunaigat AN, Smadi S, Sawaqed R, Perkins D, Shahrara S, Sweiss NJ (2014) Tocilizumab in the treatment of rheumatoid arthritis and beyond. Drug Des Devel Ther 8:349–364PubMedPubMedCentral
212.
Shibata Y, Berclaz PY, Chroneos ZC, Yoshida M, Whitsett JA, Trapnell BC (2001) GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1. Immunity 15:557–567PubMedCrossRef
213.
Shiomi A, Usui T (2015) Pivotal roles of GM-CSF in autoimmunity and inflammation. Mediat Inflamm 2015:568543CrossRef
214.
Shiomi A, Usui T, Ishikawa Y, Shimizu M, Murakami K, Mimori T (2014) GM-CSF but not IL-17 is critical for the development of severe interstitial lung disease in SKG mice. J Immunol 193:849–859PubMedCrossRef
215.
Sims JE, Smith DE (2010) The IL-1 family: regulators of immunity. Nat Rev Immunol 10:89–102PubMedCrossRef
216.
Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O’Dell J, Winthrop KL, Beukelman T, Bridges SL Jr, Chatham WW, Paulus HE, Suarez-Almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG (2012) 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 64:625–639CrossRef
217.
Skiniotis G, Boulanger MJ, Garcia KC, Walz T (2005) Signaling conformations of the tall cytokine receptor gp130 when in complex with IL-6 and IL-6 receptor. Nat Struct Mol Biol 12:545–551PubMedCrossRef
218.
219.
Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R (2008) Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 371:987–997PubMedCrossRef
220.
Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, Gorter S, Knevel R, Nam J, Schoels M, Aletaha D, Buch M, Gossec L, Huizinga T, Bijlsma JW, Burmester G, Combe B, Cutolo M, Gabay C, Gomez-Reino J, Kouloumas M, Kvien TK, Martin-Mola E, McInnes I, Pavelka K, van Riel P, Scholte M, Scott DL, Sokka T, Valesini G, van Vollenhoven R, Winthrop KL, Wong J, Zink A, van der Heijde D (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69:964–975PubMedPubMedCentralCrossRef
221.
Smolen JS, Weinblatt ME, Sheng S, Zhuang Y, Hsu B (2014) Sirukumab, a human anti-interleukin-6 monoclonal antibody: a randomised, 2-part (proof-of-concept and dose-finding), phase II study in patients with active rheumatoid arthritis despite methotrexate therapy. Ann Rheum Dis 73:1616–1625PubMedPubMedCentralCrossRef
222.
Stojanov S, Kastner DL (2005) Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol 17:586–599PubMedCrossRef
223.
Stosser S, Schweizerhof M, Kuner R (2011) Hematopoietic colony-stimulating factors: new players in tumor-nerve interactions. J Mol Med (Berl) 89:321–329CrossRef
224.
Sugarman BJ, Aggarwal BB, Hass PE, Figari IS, Palladino MA Jr, Shepard HM (1985) Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science 230:943–945PubMedCrossRef
225.
Suzuki M, Hashizume M, Yoshida H, Mihara M (2010) Anti-inflammatory mechanism of tocilizumab, a humanized anti-IL-6R antibody: effect on the expression of chemokine and adhesion molecule. Rheumatol Int 30:309–315PubMedCrossRef
226.
Suzuki M, Hashizume M, Yoshida H, Shiina M, Mihara M (2010) IL-6 and IL-1 synergistically enhanced the production of MMPs from synovial cells by up-regulating IL-6 production and IL-1 receptor I expression. Cytokine 51:178–183PubMedCrossRef
227.
Tanaka Y, Martin Mola E (2014) IL-6 targeting compared to TNF targeting in rheumatoid arthritis: studies of olokizumab, sarilumab and sirukumab. Ann Rheum Dis 73:1595–1597PubMedCrossRef
228.
Tarnowski M, Paradowska-Gorycka A, Dabrowska-Zamojcin E, Czerewaty M, Sluczanowska-Glabowska S, Pawlik A (2016) The effect of gene polymorphisms on patient responses to rheumatoid arthritis therapy. Expert Opin Drug Metab Toxicol 12:41–55PubMedCrossRef
229.
Taylor PC, Peters AM, Paleolog E, Chapman PT, Elliott MJ, McCloskey R, Feldmann M, Maini RN (2000) Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis. Arthritis Rheum 43:38–47PubMedCrossRef
230.
Thompson C, Davies R, Choy E (2016) Anti cytokine therapy in chronic inflammatory arthritis. Cytokine 86:92–99PubMedCrossRef
231.
Toh ML, Gonzales G, Koenders MI, Tournadre A, Boyle D, Lubberts E, Zhou Y, Firestein GS, van den Berg WB, Miossec P (2010) Role of interleukin 17 in arthritis chronicity through survival of synoviocytes via regulation of synoviolin expression. PLoS One 5:e13416PubMedPubMedCentralCrossRef
232.
Toh ML, Kawashima M, Hot A, Miossec P (2010) Role of IL-17 in the Th1 systemic defects in rheumatoid arthritis through selective IL-12Rbeta2 inhibition. Ann Rheum Dis 69:1562–1567PubMedCrossRef
233.
Toy D, Kugler D, Wolfson M, Vanden Bos T, Gurgel J, Derry J, Tocker J, Peschon J (2006) Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol 177:36–39PubMedCrossRef
234.
Uchiyama Y, Yorozu K, Hashizume M, Moriya Y, Mihara M (2008) Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorates joint swelling in established monkey collagen-induced arthritis. Biol Pharm Bull 31:1159–1163PubMedCrossRef
235.
Ulfgren AK, Grondal L, Lindblad S, Khademi M, Johnell O, Klareskog L, Andersson U (2000) Interindividual and intra-articular variation of proinflammatory cytokines in patients with rheumatoid arthritis: potential implications for treatment. Ann Rheum Dis 59:439–447PubMedPubMedCentralCrossRef
236.
van de Loo FA, Joosten LA, van Lent PL, Arntz OJ, van den Berg WB (1995) Role of interleukin-1, tumor necrosis factor alpha, and interleukin-6 in cartilage proteoglycan metabolism and destruction. Effect of in situ blocking in murine antigen- and zymosan-induced arthritis. Arthritis Rheum 38:164–172PubMedCrossRef
237.
van der Meer JW, Barza M, Wolff SM, Dinarello CA (1988) A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci U S A 85:1620–1623PubMedPubMedCentralCrossRef
238.
Van Lent PL, Van De Loo FA, Holthuysen AE, Van Den Bersselaar LA, Vermeer H, Van Den Berg WB (1995) Major role for interleukin 1 but not for tumor necrosis factor in early cartilage damage in immune complex arthritis in mice. J Rheumatol 22:2250–2258PubMed
239.
van Nieuwenhuijze A, Koenders M, Roeleveld D, Sleeman MA, van den Berg W, Wicks IP (2013) GM-CSF as a therapeutic target in inflammatory diseases. Mol Immunol 56:675–682PubMedCrossRef
240.
van Nieuwenhuijze AE, van de Loo FA, Walgreen B, Bennink M, Helsen M, van den Bersselaar L, Wicks IP, van den Berg WB, Koenders MI (2015) Complementary action of granulocyte macrophage colony-stimulating factor and interleukin-17A induces interleukin-23, receptor activator of nuclear factor-kappaB ligand, and matrix metalloproteinases and drives bone and cartilage pathology in experimental arthritis: rationale for combination therapy in rheumatoid arthritis. Arthritis Res Ther 17:163PubMedPubMedCentralCrossRef
241.
Wallis RS (2008) Tumour necrosis factor antagonists: structure, function, and tuberculosis risks. Lancet Infect Dis 8:601–611PubMedCrossRef
242.
Weinblatt ME, Mease P, Mysler E, Takeuchi T, Drescher E, Berman A, Xing J, Zilberstein M, Banerjee S, Emery P (2015) The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate: results from a multinational, phase IIb, randomized, double-blind, placebo/active-controlled, dose-ranging study. Arthritis Rheumatol 67:2591–2600PubMedCrossRef
243.
Wicks IP, Roberts AW (2016) Targeting GM-CSF in inflammatory diseases. Nat Rev Rheumatol 12:37–48PubMedCrossRef
244.
Williams RO, Feldmann M, Maini RN (1992) Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A 89:9784–9788PubMedPubMedCentralCrossRef
245.
Wooley PH, Dutcher J, Widmer MB, Gillis S (1993) Influence of a recombinant human soluble tumor necrosis factor receptor FC fusion protein on type II collagen-induced arthritis in mice. J Immunol 151:6602–6607PubMed
246.
Xu WD, Firestein GS, Taetle R, Kaushansky K, Zvaifler NJ (1989) Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest 83:876–882PubMedPubMedCentralCrossRef
247.
Yang YH, Hamilton JA (2001) Dependence of interleukin-1-induced arthritis on granulocyte-macrophage colony-stimulating factor. Arthritis Rheum 44:111–119PubMedCrossRef
248.
Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, Nakahata T, Kawai H, Tagoh H, Komori T et al (1989) Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood 74:1360–1367PubMed
249.
Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H, Maslinski W (2000) High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J Immunol 164:2832–2838PubMedCrossRef
250.
Zrioual S, Toh ML, Tournadre A, Zhou Y, Cazalis MA, Pachot A, Miossec V, Miossec P (2008) IL-17RA and IL-17RC receptors are essential for IL-17A-induced ELR+ CXC chemokine expression in synoviocytes and are overexpressed in rheumatoid blood. J Immunol 180:655–663PubMedCrossRef
Metadaten
Titel
Selected cytokine pathways in rheumatoid arthritis
verfasst von
Mélissa Noack
Pierre Miossec
Publikationsdatum
17.02.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Seminars in Immunopathology / Ausgabe 4/2017
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-017-0619-z

Weitere Artikel der Ausgabe 4/2017

Seminars in Immunopathology 4/2017 Zur Ausgabe

Review

Arthritis models: usefulness and interpretation

Review

Environmental factors and hormones in the development of rheumatoid arthritis

Review

Future therapeutic targets in rheumatoid arthritis?

Review

Synovial cellular and molecular markers in rheumatoid arthritis

Review

Genetics of rheumatoid arthritis susceptibility, severity, and treatment response

Review

Epigenetics in the pathogenesis of RA

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise