nach oben

Rheumatology International

Erschienen in:

01.12.2007 | Original Article

Etanercept reduces the serum levels of interleukin-23 and macrophage inflammatory protein-3 alpha in patients with rheumatoid arthritis

verfasst von: Yasunori Kageyama, Tetsuya Ichikawa, Tetsuyuki Nagafusa, Eiji Torikai, Masahiro Shimazu, Akira Nagano

Erschienen in: Rheumatology International | Ausgabe 2/2007

Einloggen, um Zugang zu erhalten

Abstract

The purpose of this study was to analyze the effect of the soluble TNF-α receptor etanercept on the serum levels of IL-16, IL-17, IL-23, and macrophage inflammatory protein-3α (MIP-3α) in rheumatoid arthritis (RA) patients. Twenty-two patients with RA were administered etanercept once or twice a week for more than 6 months, and we evaluated clinical and laboratory parameters and serum levels of IL-16, IL-17, IL-23, and MIP-3α at the baseline and at 3 and 6 months. Additionally, the production of IL-23 and MIP-3α of cultured synovial cells stimulated with TNF-α from RA patients was determined by ELISA. We also used ELISA kits to determine synovial fluid (SF) levels of IL-17, IL-23, and MIP-3α in patients with RA, osteoarthritis (OA), pseudogouty arthritis (PGA), and gouty arthritis (GA). A significant decrease in serum levels of IL-23 and MIP-3α was observed at 3 and 6 months after initial treatment of etanercept. TNF-α induced MIP-3α but not IL-23 production in cultured synovial cells from RA patients. SF levels of IL-17, IL-23, and MIP-3α in RA patients showed significantly higher levels than those of OA, PGA, and GA patients. This study demonstrated that the reduction of IL-23 and MIP-3α production in RA patients was a newly determined function of etanercept

Arend WP, Dayer J-M (1995) Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis Rheum 38:151–160PubMedCrossRef

Maini RN, Taylor PC (2000) Anti-cytokine therapy for rheumatoid arthritis. Annu Rev Med 51:207–229PubMedCrossRef

Woo CH, Kim TH, Choi JA, Ryu HC, Lee JE, You HJ, Bae YS, Kim JH (2006) Inhibition of receptor internalization attenuates the TNF alpha-induced ROS generation in non-phagocytic cells. Biochem Biophys Res Commun 351:972–978PubMedCrossRef

Sakon S, Xue X, Takekawa M, Sasazuki T, Okazaki T, Kojima Y, Piao JH, Yagita H, Okumura K, Doi T, Nakano H (2003) NF-kappa B inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J 22:3898–3909PubMedCrossRef

Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN (1998) Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor alpha and interleukin-1 in rheumatoid arthritis. Arthritis Rheum 41:1258–1265PubMedCrossRef

Feldmann M, Maini RN (2001) Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol 19:163–196PubMedCrossRef

Pittoni V, Bombardieri M, Spinelli FR, Scrivo R, Alessandri C, Conti F, Spadaro A, Valesini G (2002) Anti-tumour necrosis factor (TNF) alpha treatment of rheumatoid arthritis (infliximab) selectively down regulates the production of interleukin (IL) 18 but not of IL12 and IL13. Ann Rheum Dis 61:723–725PubMedCrossRef

Klimiuk PA, Sierakowski S, Domyslawska I, Chwiecko J (2004) Effect of repeated infliximab therapy on serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with rheumatoid arthritis. J Rheumatol 31:238–242PubMed

Kageyama Y, Takahashi M, Torikai E, Suzuki M, Ichikawa T, Nagafusa T, Koide Y, Nagano A (2007) Treatment with anti-TNF-alpha antibody infliximab reduces serum IL-15 levels in patients with rheumatoid arthritis. Clin Rheumatol 26:505–509PubMedCrossRef

10.

Torikai E, Kageyama Y, Suzuki M, Ichikawa T, Nagano A (2007) The effect of infliximab on chemokines in patients with rheumatoid arthritis. Clin Rheumatol 26:1088–1093PubMedCrossRef

11.

Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR (2000) Macrophages in rheumatoid arthritis. Arthritis Res 2:189–202PubMedCrossRef

12.

Szekanecz Z, Kim J, Koch AE (2003) Chemokines and chemokine receptors in rheumatoid arthritis. Semin Immunol 15:15–21PubMedCrossRef

13.

Dieu-Nosjean MC, Massacrier C, Homey B, Vanbervliet B, Pin JJ, Vicari A, Lebecque S, Dezutter-Dambuyant C, Schmitt D, Zlotnik A, Caux C (2000) Macrophage inflammatory protein 3 alpha is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors. J Exp Med 192:705–718PubMedCrossRef

14.

Kleeff J, Kusama T, Rossi DL, Ishiwata T, Maruyama H, Friess H, Buchler MW, Zlotnik A, Korc M (1999) Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer. Int J Cancer 81:650–657PubMedCrossRef

15.

Schutyser E, Struyf S, Menten P, Lenaerts JP, Conings R, Put W, Wuyts A, Proost P, Van Damme J (2000) Regulated production and molecular diversity of human liver and activation-regulated chemokine/macrophage inflammatory protein-3 alpha from normal and transformed cells. J Immunol 165:4470–4477PubMed

16.

Chabaud M, Page G, Miossec P (2001) Enhancing effect of IL-1, IL-17, and TNF-alpha on macrophage inflammatory protein-3 alpha production in rheumatoid arthritis: regulation by soluble receptors and Th2 cytokines. J Immunol 167:6015–6020PubMed

17.

Murphy CA, Langrish CL, Chen Y, Blumenschein W, McClanahan T, Kastelein RA, Sedgwick JD, Cua DJ (2003) Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 198:1951–1957PubMedCrossRef

18.

Gottlieb AB, Chamian F, Masud S, Cardinale I, Abello MV, Lowes MA, Chen F, Magliocco M, Krueger JG (2005) TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol 175:2721–2729PubMed

19.

Cho ML, Kang JW, Moon YM, Nam HJ, Jhun JY, Heo SB, Jin HT, Min SY, Ju JH, Park KS, Cho YG, Yoon CH, Park SH, Sung YC, Kim HY (2006) STAT3 and NF-B signal pathway is required for IL-23-mediated IL-17 production in spontaneous arthritis animal model IL-1 receptor antagonist-deficient mice. J Immunol 176:5652–5661PubMed

20.

Hoeve MA, Savage ND, de Boer T, Langenberg DM, de Waal Malefyt R, Ottenhoff TH, Verreck FA (2006) Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. Eur J Immunol 36:661–670PubMedCrossRef

21.

Glabinski AR, Bielecki B, Kawczak JA, Tuohy VK, Selmaj K, Ransohoff RM (2004) Treatment with soluble tumor necrosis factor receptor (sTNFR):Fc/p80 fusion protein ameliorates relapsing-remitting experimental autoimmune encephalomyelitis and decreases chemokine expression. Autoimmunity 37:465–471PubMedCrossRef

22.

Madhusudan S, Foster M, Muthuramalingam SR, Braybrooke JP, Wilner S, Kaur K, Han C, Hoare S, Balkwill F, Talbot DC, Ganesan TS, Harris AL (2004) A phase II study of etanercept (Enbrel), a tumor necrosis factor alpha inhibitor in patients with metastatic breast cancer. Clin Cancer Res 10:6528–6534PubMedCrossRef

23.

Catrina AI, Lampa J, Ernestam S, af Klint E, Bratt J, Klareskog L, Ulfgren AK (2002) Anti-tumour necrosis factor (TNF)-alpha therapy (etanercept) down-regulates serum matrix metalloproteinase (MMP)-3 and MMP-1 in rheumatoid arthritis. Rheumatology (Oxford) 41:484–489CrossRef

24.

Kikly K, Liu L, Na S, Sedgwick JD (2006) The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 18:670–675PubMedCrossRef

25.

Chen Y, Langrish CL, McKenzie B, Joyce-Shaikh B, Stumhofer JS, McClanahan T, Blumenschein W, Churakovsa T, Low J, Presta L, Hunter CA, Kastelein RA, Cua DJ (2006) Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest 116:1317–1326PubMedCrossRef

26.

Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748PubMedCrossRef

27.

Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103:1345–1352PubMedCrossRef

28.

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

29.

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 164:2832–2838PubMed

30.

Happel KI, Zheng M, Young E, Quinton LJ, Lockhart E, Ramsay AJ, Shellito JE, Schurr JR, Bagby GJ, Nelson S, Kolls JK (2003) Cutting edge: roles of Toll-like receptor 4 and IL-23 in IL-17 expression in response to Klebsiella pneumoniae infection. J Immunol 170:4432–4436PubMed

31.

Sheibanie AF, Tadmori I, Jing H, Vassiliou E, Ganea D (2004) Prostaglandin E2 induces IL-23 production in bone marrow-derived dendritic cells. FASEB J 18:1318–1320PubMed

32.

Lee HJ, Choi SC, Lee MH, Oh HM, Choi EY, Choi EJ, Yun KJ, Seo GS, Kim SW, Lee JG, Han WC, Park KI, Jun CD (2005) Increased expression of MIP-3alpha/CCL20 in peripheral blood mononuclear cells from patients with ulcerative colitis and its down-regulation by sulfasalazine and glucocorticoid treatment. Inflamm Bowel Dis 11:1070–1079PubMedCrossRef

33.

Baba M, Imai T, Nishimura M, Kakizaki M, Takagi S, Hieshima K, Nomiyama H, Yoshie O (1997) Identification of CCR6, the specific receptor for a novel lymphocyte-directed CC chemokine LARC. J Biol Chem 272:14893–14898PubMedCrossRef

34.

Power CA, Church DJ, Meyer A, Alouani S, Proudfoot AE, Clark-Lewis I, Sozzani S, Mantovani A, Wells TN (1997) Cloning and characterization of a specific receptor for the novel CC chemokine MIP-3alpha from lung dendritic cells. J Exp Med 186:825–835PubMedCrossRef

35.

Akahoshi T, Sasahara T, Namai R, Matsui T, Watabe H, Kitasato H, Inoue M, Kondo H (2003) Production of macrophage inflammatory protein 3 alpha (MIP-3alpha) (CCL20) and MIP-3beta (CCL19) by human peripheral blood neutrophils in response to microbial pathogens. Infect Immun 71:524–526PubMedCrossRef

36.

Vanbervliet B, Homey B, Durand I, Massacrier C, Ait-Yahia S, de Bouteiller O, Vicari A, Caux C (2002) Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces. Eur J Immunol 32:231–242PubMedCrossRef

37.

Greaves DR, Wang W, Dairaghi DJ, Dieu MC, Saint-Vis B, Franz-Bacon K, Rossi D, Caux C, McClanahan T, Gordon S, Zlotnik A, Schall TJ (1997) CCR6, a CC chemokine receptor that interacts with macrophage inflammatory protein 3 alpha and is highly expressed in human dendritic cells. J Exp Med 186:837–844PubMedCrossRef

38.

Matsui T, Akahoshi T, Namai R, Hashimoto A, Kurihara Y, Rana M, Nishimura A, Endo H, Kitasato H, Kawai S, Takagishi K, Kondo H (2001) Selective recruitment of CCR6-expressing cells by increased production of MIP-3 alpha in rheumatoid arthritis. Clin Exp Immunol 125:155–161PubMedCrossRef

39.

Szekanecz Z, Strieter RM, Kunkel SL, Koch AE (1998) Chemokines in rheumatoid arthritis. Springer Semin Immunopathol 20:115–132PubMedCrossRef

40.

Chevrel G, Garnero P, Miossec P (2002) Addition of interleukin-1 (IL1) and IL17 soluble receptors to a tumour necrosis factor soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3 and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation. Ann Rheum Dis 61:730–733PubMedCrossRef

41.

Sugita S, Kohno T, Yamamoto K, Imaizumi Y, Nakajima H, Ishimaru T, Matsuyama T (2002) Induction of macrophage-inflammatory protein-3 alpha gene expression by TNF-dependent NF-kappaB activation. J Immunol 168:5621–5628PubMed

42.

Lisignoli G, Piacentini A, Cristino S, Grassi F, Cavallo C, Cattini L, Tonnarelli B, Manferdini C, Facchini A (2007) CCL20 chemokine induces both osteoblast proliferation and osteoclast differentiation: Increased levels of CCL20 are expressed in subchondral bone tissue of rheumatoid arthritis patients. J Cell Physiol 210:798–806PubMedCrossRef

43.

Franz JK, Kolb SA, Hummel KM, Lahrtz F, Neidhart M, Aicher WK, Pap T, Gay RE, Fontana A, Gay S (1998) Interleukin-16, produced by synovial fibroblasts, mediates chemoattraction for CD4+ T lymphocytes in rheumatoid arthritis. Eur J Immunol 28:2661–2671PubMedCrossRef

44.

Klimiuk PA, Goronzy JJ, Weyand CM (1999) IL-16 as an anti-inflammatory cytokine in rheumatoid synovitis. J Immunol 162:4293–4299PubMed

45.

Atkins GJ, Haynes DR, Geary SM, Loric M, Crotti TN, Findlay DM (2000) Coordinated cytokine expression by stromal and hematopoietic cells during human osteoclast formation. Bone 26:653–661PubMedCrossRef

Titel: Etanercept reduces the serum levels of interleukin-23 and macrophage inflammatory protein-3 alpha in patients with rheumatoid arthritis
verfasst von: Yasunori Kageyama
Tetsuya Ichikawa
Tetsuyuki Nagafusa
Eiji Torikai
Masahiro Shimazu
Akira Nagano
Publikationsdatum: 01.12.2007
Verlag: Springer-Verlag
Erschienen in: Rheumatology International / Ausgabe 2/2007
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-007-0388-4

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

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2007

A novel mutation of the familial Mediterranean fever gene in a Greek family related to a non-classical, variably expressed FMF phenotype

Hodgkin’s lymphoma following treatment with etanercept in ankylosing spondylitis

Tumor necrosis factor alpha −308 polymorphism is associated with rheumatoid arthritis in Han population of Eastern China

Measurement of advanced glycation endproducts in skin of patients with rheumatoid arthritis, osteoarthritis, and dialysis-related spondyloarthropathy using non-invasive methods

The association of DRB1*04 share epitope alleles and tumor necrosis factor-alpha gene polymorphism (−863) with susceptibility to rheumatoid arthritis in Thai