Statins and autoimmunity

Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990;343(6257):425–30. Shovman O, Levy Y, Gilburd B, Shoenfeld Y. Antiinflammatory and immunomodulatory properties of statins. Immunol Res. 2002;25:271–85. 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. 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. 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. 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. Abou-Raya A, Abou-Raya S, Helmii M. Statins as immunomodulators in systemic sclerosis. Ann N Y Acad Sci. 2007;1110:670–80. 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. 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. Tristano AG, Fuller K. Immunomodulatory effects of statins and autoimmune rheumatic diseases: novel intracellular mechanism involved. Int Immunopharmacol. 2006;6:1833–46. Greenwood J, Steinman L, Zamvil SS. Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat Rev Immunol. 2006;6:358–70. 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. 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. 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. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–19. 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. 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. Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A. Non-lipid-related effects of statins. Ann Med. 2000;32:164–76. Roman-Blas JA, Jimenez SA. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthr Cartil. 2006;14:839–48. Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397–440. 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. 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. Takai Y, Sasaki T, Matozaki T. Small GTP-binding proteins. Physiol Rev. 2001;81:153–208. Liao JK. Isoprenoids as mediators of the biological effects of statins. J Clin Invest. 2002;110:285–8. Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol. 2005;45:89–118. 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. 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. 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. Van Doornum S, McColl G, Wicks IP. Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis. Ann Rheum Dis. 2004;63:1571–5. Heymann AD, Porath A, et al. Persistence with statins and onset of rheumatoid arthritis: a population-based cohort study. PLoS Med. 2010;7:e1000336. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Scoble T, Wijetilleka S, Khamashta MA. Management of refractory anti-phospholipid syndrome. Autoimmun Rev. 2011;10:669–73. 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. 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. 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. 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. 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. 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. Naoe S, Takahashi K, Masuda H, Tanaka N. Kawasaki disease with particular emphasis on arterial lesions. Acta Pathol Jpn. 1991;41:785–97. 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. 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. 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. 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. Urowitz M, Gladman D, Bruce I. Atherosclerosis and systemic lupus erythematosus. Curr Rheumatol Rep. 2000;2:19–23. 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. 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. 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. 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. Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol. 2008;26(5 Suppl 51):S35–61. 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. 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. 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. 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. 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. 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. 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. 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. Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol. 2011;7:399–408. Dalakas MC. Pathogenesis and therapies of immune-mediated myopathies. Autoimmun Rev. 2012;11:203–6. 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.