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
Immunologic Research
Erschienen in: Immunologic Research 2-3/2013

01.07.2013 | Treatment of Autoimmunity

Statins and autoimmunity

verfasst von: Saakshi Khattri, Gisele Zandman-Goddard

Erschienen in: Immunologic Research | Ausgabe 2-3/2013

Einloggen, um Zugang zu erhalten

Abstract

Statins have immunomodulatory effects. Hence, they could be advantageous for different reasons. First, statins can serve as adjunct therapy in autoimmune diseases. Second, they may play a role in the prevention of accelerated atherosclerosis in the same population. In this review, we discuss the mechanisms of immune regulation by statins and review the literature for their benefit in many autoimmune diseases. In these studies, statins lead to an improvement in the disease activity scores in rheumatoid arthritis patients; a reduction in prothrombotic factors in anti-phospholipid syndrome patients; changes in vasculature, proteinuria, and cardiac events in systemic lupus erythematosus patients; changes in vasculature and proteinuria in patients with vasculitis; disease activity scores in ankylosing spondylitis; and finally vascular changes in patients with systemic sclerosis. Hence, these studies suggest that statins could be used as adjuncts to standard therapy due to their anti-inflammatory, immunomodulatory, and anti-thrombogenic effects. More evidence-based research is required to determine whether statin regimens will become the standard of care in patients with autoimmune diseases.
Literatur
1.
Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990;343(6257):425–30.PubMedCrossRef
2.
Shovman O, Levy Y, Gilburd B, Shoenfeld Y. Antiinflammatory and immunomodulatory properties of statins. Immunol Res. 2002;25:271–85.PubMedCrossRef
3.
Youssef S, Stuve O, Patarroyo JC, Ruiz PJ, Radosevich JL, Hur EM, et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature. 2002;420:78–84.PubMedCrossRef
4.
Sparrow CP, Burton CA, Hernandez M, Mundt S, Hassing H, Patel S, et al. Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arterioscler Thromb Vasc Biol. 2001;21:115–21.PubMedCrossRef
5.
Kobashigawa JA, Katznelson S, Laks H, Johnson JA, Yeatman L, Wang XM, et al. Effect of pravastatin on outcomes after cardiac transplantation. N Engl J Med. 1995;333:621–7.PubMedCrossRef
6.
McCarey DW, McInnes IB, Madhok R, Hampson R, Scherbakov O, Ford I, et al. Trial of Atorvastatin in Rheumatoid Arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet. 2004;363:2015–21.PubMedCrossRef
7.
Abou-Raya A, Abou-Raya S, Helmii M. Statins as immunomodulators in systemic sclerosis. Ann N Y Acad Sci. 2007;1110:670–80.PubMedCrossRef
8.
Abou-Raya A, Abou-Raya S, Helmii M. Statins: potentially useful in therapy of systemic sclerosis-related Raynaud’s phenomenon and digital ulcers. J Rheumatol. 2008;35:1801–8.PubMed
9.
Ferreira GA, Navarro TP, Telles RW, Andrade LE, Sato EI. Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial. Rheumatology (Oxford). 2007;46:1560–5.CrossRef
10.
Tristano AG, Fuller K. Immunomodulatory effects of statins and autoimmune rheumatic diseases: novel intracellular mechanism involved. Int Immunopharmacol. 2006;6:1833–46.PubMedCrossRef
11.
Greenwood J, Steinman L, Zamvil SS. Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat Rev Immunol. 2006;6:358–70.PubMedCrossRef
12.
Zhang X, Jin J, Peng X, Ramgolam VS, Markovic-Plese S. Simvastatin inhibits IL-17 secretion by targeting multiple IL-17-regulatory cytokines and by inhibiting the expression of IL-17 transcription factor RORC in CD4+ lymphocytes. J Immunol. 2008;180:6988–96.PubMed
13.
Ghittoni R, Napolitani G, Benati D, Ulivieri C, Patrussi L. Laghi Pasini F et al. Simvastatin inhibits the MHC class II pathway of antigen presentation by impairing Ras superfamily GTPases. Eur J Immunol. 2006;36:2885–93.PubMedCrossRef
14.
Dunn SE, Youssef S, Goldstein MJ, Prod’homme T, Weber MS, Zamvil SS, et al. Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin. J Exp Med. 2006;203:401–12.PubMedCrossRef
15.
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–19.PubMedCrossRef
16.
Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, et al. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med. 2001;7:687–92.PubMedCrossRef
17.
Meroni PL, Luzzana C, Ventura D. Anti-inflammatory and immunomodulating properties of statins. An additional tool for the therapeutic approach of systemic autoimmune diseases? Clin Rev Allergy Immunol. 2002;23:263–77.PubMedCrossRef
18.
Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A. Non-lipid-related effects of statins. Ann Med. 2000;32:164–76.PubMedCrossRef
19.
Roman-Blas JA, Jimenez SA. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthr Cartil. 2006;14:839–48.PubMedCrossRef
20.
Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397–440.PubMedCrossRef
21.
Chinetti G, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res. 2000;49:497–505.PubMedCrossRef
22.
Cernuda-Morollon E, Rodriguez-Pascual F, Klatt P, Lamas S, Perez-Sala D. PPAR agonists amplify iNOS expression while inhibiting NF-kappaB: implications for mesangial cell activation by cytokines. J Am Soc Nephrol. 2002;13:2223–31.PubMedCrossRef
23.
Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev. 2001;81:153–208.PubMed
24.
Liao JK. Isoprenoids as mediators of the biological effects of statins. J Clin Invest. 2002;110:285–8.PubMed
25.
Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89–118.PubMedCrossRef
26.
Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, et al. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol. 2003;170:1524–30.PubMed
27.
Yamagata T, Kinoshita K, Nozaki Y, Sugiyama M, Ikoma S, Funauchi M. Effects of pravastatin in murine collagen-induced arthritis. Rheumatol Int. 2007;27:631–9.PubMedCrossRef
28.
Maki-Petaja KM, Booth AD, Hall FC, Wallace SM, Brown J, McEniery CM, et al. Ezetimibe and simvastatin reduce inflammation, disease activity, and aortic stiffness and improve endothelial function in rheumatoid arthritis. J Am Coll Cardiol. 2007;50:852–8.PubMedCrossRef
29.
Van Doornum S, McColl G, Wicks IP. Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis. Ann Rheum Dis. 2004;63:1571–5.PubMedCrossRef
30.
Heymann AD, Porath A, et al. Persistence with statins and onset of rheumatoid arthritis: a population-based cohort study. PLoS Med. 2010;7:e1000336.PubMedCrossRef
31.
Tang TT, Song Y, Ding YJ, Liao YH, Yu X, Du R, et al. Atorvastatin upregulates regulatory T cells and reduces clinical disease activity in patients with rheumatoid arthritis. J Lipid Res. 2011;52:1023–32.PubMedCrossRef
32.
El-Barbary AM, Hussein MS, Rageh EM, Hamouda HE, Wagih AA, Ismail RG. Effect of atorvastatin on inflammation and modification of vascular risk factors in rheumatoid arthritis. J Rheumatol. 2011;38:229–35.PubMedCrossRef
33.
Abud-Mendoza C, de la Fuente H, Cuevas-Orta E, Baranda L, Cruz-Rizo J, Gonzalez-Amaro R. Therapy with statins in patients with refractory rheumatic diseases: a preliminary study. Lupus. 2003;12:607–11.PubMedCrossRef
34.
Ferrara DE, Liu X, Espinola RG, Meroni PL, Abukhalaf I, Harris EN, et al. Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model. Arthritis Rheum. 2003;48:3272–9.PubMedCrossRef
35.
Meroni PL, Raschi E, Testoni C, Tincani A, Balestrieri G, Molteni R, et al. Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. Arthritis Rheum. 2001;44:2870–8.PubMedCrossRef
36.
Ferrara DE, Swerlick R, Casper K, Meroni PL, Vega-Ostertag ME, Harris EN, et al. Fluvastatin inhibits up-regulation of tissue factor expression by antiphospholipid antibodies on endothelial cells. J Thromb Haemost. 2004;2:1558–63.PubMedCrossRef
37.
Jajoria P, Murthy V, Papalardo E, Romay-Penabad Z, Gleason C, Pierangeli SS. Statins for the treatment of antiphospholipid syndrome? Ann N Y Acad Sci. 2009;1173:736-45.
38.
Lopez-Pedrera C, Ruiz-Limon P, Aguirre MA, Barbarroja N, Perez-Sanchez C, Buendia P, et al. Global effects of fluvastatin on the prothrombotic status of patients with antiphospholipid syndrome. Ann Rheum Dis. 2011;70:675–82.PubMedCrossRef
39.
Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, Brey R, Crowther M, Derksen R, et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th international congress on antiphospholipid antibodies. Lupus. 2011;20:206–18.PubMedCrossRef
40.
Guyatt GH, Cook DJ, Jaeschke R, Pauker SG, Schunemann HJ. Grades of recommendation for antithrombotic agents: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest. 2008;133(6 Suppl):123S–31S.PubMedCrossRef
41.
Scoble T, Wijetilleka S, Khamashta MA. Management of refractory anti-phospholipid syndrome. Autoimmun Rev. 2011;10:669–73.PubMedCrossRef
42.
Glynn RJ, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851–61.PubMedCrossRef
43.
Lawman S, Mauri C, Jury EC, Cook HT, Ehrenstein MR. Atorvastatin inhibits autoreactive B cell activation and delays lupus development in New Zealand black/white F1 mice. J Immunol. 2004;173:7641–6.PubMed
44.
Shimazu H, Kinoshita K, Hino S, Yano T, Kishimoto K, Nagare Y, et al. Effect of combining ACE inhibitor and statin in lupus-prone mice. Clin Immunol. 2010;136:188–96.PubMedCrossRef
45.
Aprahamian T, Bonegio R, Rizzo J, Perlman H, Lefer DJ, Rifkin IR, et al. Simvastatin treatment ameliorates autoimmune disease associated with accelerated atherosclerosis in a murine lupus model. J Immunol. 2006;177:3028–34.PubMed
46.
Norby GE, Holme I, Fellstrom B, Jardine A, Cole E, Abedini S, et al. Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: a randomized placebo-controlled study. Arthritis Rheum. 2009;60:1060–4.PubMedCrossRef
47.
Blankier S, McCrindle BW, Ito S, Yeung RS. The role of atorvastatin in regulating the immune response leading to vascular damage in a model of Kawasaki disease. Clin Exp Immunol. 2011;164:193–201.PubMedCrossRef
48.
Naoe S, Takahashi K, Masuda H, Tanaka N. Kawasaki disease with particular emphasis on arterial lesions. Acta Pathol Jpn. 1991;41:785–97.PubMed
49.
Hamaoka A, Hamaoka K, Yahata T, Fujii M, Ozawa S, Toiyama K, et al. Effects of HMG-CoA reductase inhibitors on continuous post-inflammatory vascular remodeling late after Kawasaki disease. J Cardiol. 2010;56:245–53.PubMedCrossRef
50.
van Denderen JC, Peters MJ, van Halm VP, van der Horst-Bruinsma IE, Dijkmans BA, Nurmohamed MT. Statin therapy might be beneficial for patients with ankylosing spondylitis. Ann Rheum Dis. 2006;65:695–6.PubMedCrossRef
51.
Louneva N, Huaman G, Fertala J, Jimenez SA. Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin. Arthritis Rheum. 2006;54:1298–308.PubMedCrossRef
52.
Furukawa S, Yasuda S, Amengual O, Horita T, Atsumi T, Koike T. Protective effect of pravastatin on vascular endothelium in patients with systemic sclerosis: a pilot study. Ann Rheum Dis. 2006;65:1118–20.PubMedCrossRef
53.
Urowitz M, Gladman D, Bruce I. Atherosclerosis and systemic lupus erythematosus. Curr Rheumatol Rep. 2000;2:19–23.PubMedCrossRef
54.
Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003;349:2399–406.PubMedCrossRef
55.
Roman MJ, Crow MK, Lockshin MD, Devereux RB, Paget SA, Sammaritano L, et al. Rate and determinants of progression of atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2007;56:3412–9.PubMedCrossRef
56.
Costenbader KH, Liang MH, Chibnik LB, Aizer J, Kwon H, Gall V, et al. A pravastatin dose-escalation study in systemic lupus erythematosus. Rheumatol Int. 2007;27:1071–7.PubMedCrossRef
57.
Mok CC, Wong CK, To CH, Lai JP, Lam CS. Effects of rosuvastatin on vascular biomarkers and carotid atherosclerosis in lupus: a randomized, double-blind, placebo-controlled trial. Arthritis Care Res (Hoboken). 2011;63:875–83.CrossRef
58.
Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol. 2008;26(5 Suppl 51):S35–61.PubMed
59.
Esdaile JM, Abrahamowicz M, Grodzicky T, Li Y, Panaritis C, du Berger R, et al. Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum. 2001;44:2331–7.PubMedCrossRef
60.
Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how “high-grade” systemic inflammation accelerates vascular risk in rheumatoid arthritis. Circulation. 2003;108:2957–63.PubMedCrossRef
61.
Gonzalez-Gay MA, Gonzalez-Juanatey C, Pineiro A, Garcia-Porrua C, Testa A, Llorca J. High-grade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. J Rheumatol. 2005;32:1219–23.PubMed
62.
Goodson NJ, Symmons DP, Scott DG, Bunn D, Lunt M, Silman AJ. Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort. Arthritis Rheum. 2005;52:2293–9.PubMedCrossRef
63.
Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836–43.PubMedCrossRef
64.
Goodson NJ, Wiles NJ, Lunt M, Barrett EM, Silman AJ, Symmons DP. Mortality in early inflammatory polyarthritis: cardiovascular mortality is increased in seropositive patients. Arthritis Rheum. 2002;46:2010–9.PubMedCrossRef
65.
Gonzalez A, Icen M, Kremers HM, Crowson CS, Davis JM 3rd, Therneau TM, et al. Mortality trends in rheumatoid arthritis: the role of rheumatoid factor. J Rheumatol. 2008;35:1009–14.PubMedCrossRef
66.
Lopez-Longo FJ, Sanchez-Ramon S, Carreno L. The value of anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis: do they imply new risk factors? Drug News Perspect. 2009;22:543–8.PubMedCrossRef
67.
Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol. 2011;7:399–408.PubMedCrossRef
68.
Dalakas MC. Pathogenesis and therapies of immune-mediated myopathies. Autoimmun Rev. 2012;11:203–6.PubMedCrossRef
69.
Rubin G, Haddad E, Ben-Haim T, Elmalach I, Rozen N. Bilateral, simultaneous rupture of the quadriceps tendon associated with simvastatin. Isr Med Assoc J. 2011;13:185–6.PubMed
Metadaten
Titel
Statins and autoimmunity
verfasst von
Saakshi Khattri
Gisele Zandman-Goddard
Publikationsdatum
01.07.2013
Verlag
Springer-Verlag
Erschienen in
Immunologic Research / Ausgabe 2-3/2013
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-013-8409-8

Weitere Artikel der Ausgabe 2-3/2013

Immunologic Research 2-3/2013 Zur Ausgabe

Treatment of Autoimmunity

Pharmacogenetics and pharmacogenomics in rheumatology

Treatment of Autoimmunity

Refractory pemphigus foliaceus and Behçet’s disease successfully treated with tocilizumab

Diagnosis of Autoimmunity

Detecting multiple autoantibodies to diagnose autoimmune co-morbidity (multiple autoimmune syndromes and overlap syndromes): a challenge for the autoimmunologist

ETIO PATHOGENESIS OF AUTOIMMUNITY

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA syndrome) in commercial sheep

ETIO PATHOGENESIS OF AUTOIMMUNITY

Genetics and autoantibodies

Diagnosis of Autoimmunity

Complement and autoimmunity

Neu im Fachgebiet HNO

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.

HNO-Op. auch mit über 90?

16.04.2024 HNO-Chirurgie Nachrichten

Mit Blick auf das Risiko für Komplikationen nach elektiven Eingriffen im HNO-Bereich scheint das Alter der Patienten kein ausschlaggebender Faktor zu sein. Entscheidend ist offenbar, wie fit die Betroffenen tatsächlich sind.

Intrakapsuläre Tonsillektomie gewinnt an Boden

16.04.2024 Tonsillektomie Nachrichten

Gegenüber der vollständigen Entfernung der Gaumenmandeln hat die intrakapsuläre Tonsillektomie einige Vorteile, wie HNO-Fachleute aus den USA hervorheben. Sie haben die aktuelle Literatur zu dem Verfahren gesichtet.

Bilateraler Hörsturz hat eine schlechte Prognose

15.04.2024 Hörsturz Nachrichten

Die Mehrzahl der Menschen mit Hörsturz ist einseitig betroffen, doch auch ein beidseitiger Hörsturz ist möglich. Wie häufig solche Fälle sind und wie sich ihr Verlauf darstellt, hat eine HNO-Expertenrunde aus den USA untersucht.

Update HNO

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.

Newsletter bestellen
Bildnachweise