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Современная ревматология

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Роль интерлейкина 6 в развитии атеросклероза при ревматоидном артрите

https://doi.org/10.14412/1996-7012-2013-7

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Аннотация

Ревматоидный артрит (РА) – хроническое, системное аутоиммунное заболевание. Одной из основных причин смертности при РА являются сердечно-сосудистые катастрофы, обусловленные атеросклерозом сосудов. В обзоре представлены результаты исследований, посвященных изучению роли интерлейкина (ИЛ) 6 в развитии аутоиммунного воспаления и сердечно-сосудистых заболеваний. Рассмотрена связь ИЛ6, воспаления и липидного спектра крови. Уделено внимание липид-снижающему и плейотропному действию статинов. Представлены сведения о влиянии ингибиторов рецепторов ИЛ6 (тоцилизумаб – ТЦЗ) на уровень липидов крови при РА. Значение ИЛ6 в патогенезе атеросклероза при РА и влияние ТЦЗ на развитие и прогрессирование атеросклеротического процесса нуждаются в дальнейшем изучении.

Об авторах

Е. В. Удачкина
ФГБУ «Научно-исследовательский институт ревматологии им. акад. В.А. Насоновой» РАМН, Москва
Россия


Д. С. Новикова
ФГБУ «Научно-исследовательский институт ревматологии им. акад. В.А. Насоновой» РАМН, Москва
Россия


Т. В. Попкова
ФГБУ «Научно-исследовательский институт ревматологии им. акад. В.А. Насоновой» РАМН, Москва


Евгений Львович Насонов
ФГБУ «Научно-исследовательский институт ревматологии им. акад. В.А. Насоновой» РАМН, Москва


Литература

1. <div><p>Насонов ЕЛ, Каратеев ДЕ. Ревматоидный артрит. Под ред. Е.Л. Насонова, В.А. Насоновой. М.: ГЭОТАР-Медиа;2008. [Nasonov EL, Karateev DE. Revmatoidnyy artrit. Pod red. E.L. Nasonova, V.A. Nasonovoy. M.: GEOTAR-Media;2008.]</p><p>Weinblatt ME, Kuritzky L. RAPID: rheumatoid arthritis. J Fam Pract 2007;56(4 Suppl):S1–7.</p><p>Попкова ТВ, Новикова ДС, Насонов ЕЛ. Атеросклероз при ревматических заболеваниях. В кн.: Ревматология: клинические рекомендации. М.: ГЭОТАР-Медиа;2010;678–702. [Popkova TV, Novikova DS, Nasonov EL. Ateroskleroz pri revmaticheskikh zabolevaniyakh. V kn.: Revmatologiya: klinicheskie rekomendatsii. M.: GEOTAR-Media;2010;678–702.]</p><p>Peters MJ, Symmons DP, McCarey DW et al. EULAR evidence-based recomendations for cardiovascular risk management in patients with rheumatoid arthritis and other types of inflammatory arthritis — TASK FORCE «Cardiovascular risk management in RA». Ann Rheum Dis. 2010;69(2):325–31. DOI: 10.1136/ard.2009.113696. PubMed PMID: 19773290.</p><p>del Rincon I, Williams K, Stern MP et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001;44(12):2737–45. DOI: 10.1002/1529-0131(200112)44:12&lt;2737::AID-ART460&gt;3.0.CO;2-#.</p><p>Frostegard J, Ulfgren AK, Nyberg P et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis. 1999;145(1):33–43. DOI: 10.1016%2FS0021-9150%2899%2900011-8.</p><p>Skalen K, Gustafsson M, Rydberg EK et al. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature. 2002;417(6890):750–4.</p><p>Leitinger N. Oxidized phospholipids as modulators of inflammation in atherosclerosis. Curr Opin Lipidol. 2003;14(5):421–30. DOI: 10.1097%2F00041433-200310000-00002.</p><p>Frostegard J, Ulfgren AK, Nyberg P et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis. 1999;145(1):33–43. DOI: 10.1016%2FS0021-9150%2899%2900011-8.</p><p>Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685–95. DOI:10.1056%2FNEJMra043430.</p><p>Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev. 2006;86(2):515–81. DOI: 10.1152%2Fphysrev.00024.2005.</p><p>Full LE, Ruisanchez C, Monaco C. The inextricable link between atherosclerosis and prototypical inflammatory diseases rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther. 2009;11(2):217. DOI: 10.1186/ar2631. PubMed PMID: 19435478; PubMed Central PMCID: PMC2688172.</p><p>Libby P. Role of inflammation in atherosclerosis associated with rheumatoid arthritis. Am J Med. 2008;121(10 Suppl 1):S21–31. DOI: 10.1016/j.amjmed.2008.06.014.</p><p>Pasceri V, Yeh ET. A tale of two diseases: Atherosclerosis and rheumatoid arthritis. Circulation. 1999;100(21):2124–6.</p><p>Kishimoto T. The biology of interleukin-6. Blood. 1989;74:1–10.</p><p>Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994;15(2):74–80. DOI: 10.1016%2F0167-5699%2894%2990137-6.</p><p>Kishimoto T, Akira S, Narazaki M, Taga T. Interleukin-6 family of cytokines and gp 130. Blood. 1995;86:1243–54.</p><p>Danesh J, Kaptoge S, Mann A et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: Two new prospective studies and a systematic review. PLoS Med 2008;5(4):e78. DOI: 10.1371/journal.pmed.0050078.</p><p>Hoffmeister A, Rothenbacher D, Kunze M et al. Prognostic value of inflammatory markers alone and in combination with blood lipids in patients with stable coronary artery disease. Eur J Intern Med. 2005;16:47–52. DOI: 10.1016%2Fj.ejim.2004.09.008</p><p>Cesari M, Penninx BW, Newman AB et al. Inflammatory markers and cardiovascular disease (The Health, Aging and Body Composition [Health ABC] Study) Am J Cardiol. 2003;92(5):522–8.</p><p>Fisman EZ, Benderly M, Esper RJ et al. Interleukin-6 and the risk of future cardiovascular events in patients with angina pectoris and/or healed myocardial infarction. Am J Cardiol. 2006;98(1):14–8. Epub 2006 Apr 27.</p><p>Hedman A, Larsson, Thomas P et al. CRP, IL-6 and endothelin-1 levels in patients undergoing coronary artery bypass grafting. Do preoperative inflammatory parameters predict early graft occlusion and late cardiovascular events? Int J Cardiol. 2007 Aug 9;120(1):108–14. DOI: 10.1016%2Fj.ijcard.2006.09.004. Epub 2006 Dec 1.</p><p>Seino Y, Ikeda U, Ikeda M et al. Interleukin 6 gene transcripts are expressed in human atherosclerotic lesions. Cytokine. 1994 Jan;6(1):87–91. DOI: 10.1016%2F1043-4666%2894%2990013-2.</p><p>Larsson PT, Hallerstam S, Rosfors S, Wallen NH. Circulating markers of inflammation are related to carotid artery atherosclerosis. Int Angiol. 2005;24:43–51.</p><p>Amar J, Fauvel J, Drouet L et al. Interleukin 6 is associated with subclinical atherosclerosis: a link with soluble intercellular adhesion molecule 1. J Hypertens. 2006;24:1083–88. DOI: 10.1097%2F01.hjh.0000226198.44181.0c.</p><p>Okopien B, Hyper M, Kowalski J et al. A new immunological marker of atherosclerotic injury of arterial wall. Res Commun Mol Pathol Pharmacol. 2001;109(3–4):241–8.</p><p>Conway DS, Buggins P, Hughes E, Lip GY. Prognostic significance of raised plasma levels of interleukin-6 and C-reactive protein in atrial fibrillation. Am Heart J. 2004;148(3):462–6. DOI: 10.1016%2Fj.ahj.2004.01.026.</p><p>Tokunou T, Ichiki T, Takeda K et al. Thrombin induces interleukin-6 expression through the cAMP response element in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2001;21(11):1759–63. DOI: 10.1161%2Fhq1101.098489.</p><p>Williams N, Bertoncello I, Jackson H et al. The role of interleukin 6 in megakaryocyte formation, megakaryocyte development and platelet production. Ciba Found Symp. 1992;167:160–70; discussion 170-3. DOI: 10.1002%2F9780470514269.ch10.</p><p>Oleksowicz L, Mrowiec Z, Zuckerman D et al. Platelet activation induced by interleukin-6: evidence for a mechanism involving arachidonic acid metabolism. Thromb Haemost. 1994;72(2):302–8.</p><p>Burstein SA. Effects of interleukin 6 on megakaryocytes and on canine platelet function. Stem Cells. 1994;12:386–93.</p><p>Basso F, Lowe GDO, Rumley A et al. Interleukin-6 -174G&gt;C polymorphism and risk of coronary heart disease in West of Scotland coronary prevention study (WOSCOPS). Arterioscler Thromb Vasc Biol. 2002;22(4):599–604. DOI: 10.1161%2F01.ATV.0000013283.84306.1A.</p><p>Fernandez-Real JM, Broch M, Vendrell J et al. Interleukin-6 gene polymorphism and lipid abnormalities in healthy subjects. J Clin Endocrinol Metab 2000;85(3):1334–9. DOI: 10.1210%2Fjc.85.3.1334.</p><p>Berthold HK, Laudes M, Krone W, Gouni-Berthold I. Association between the Interleukin-6 Promoter Polymorphism 2174G/C and Serum Lipoprotein(a) Concentrations in Humans. PLoS ONE 2011;6(9):e24719. DOI: 10.1371/journal.pone.0024719. Epub 2011 Sep 14.</p><p>Pola R, Gaetani E, Flex A et al. -174 G/C interleukin-6 gene polymorphism and increased risk of multi-infarct dementia: a case-control study. Exp Gerontol. 2002;37(7):949–55. DOI: 10.1016%2FS0531-5565%2802%2900031-1.</p><p>Flex A, Gaetani E, Pola R et al. The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with peripheral artery occlusive disease. Eur J Vasc Endovasc Surg. 2002 Sep;24(3):264–8. DOI: 10.1053%2Fejvs.2002.1711.</p><p>Fishman D, Faulds G, Jeffery R et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102(7):1369–76. DOI: 10.1172%2FJCI2629.</p><p>Henningsson S, Hakansson A, Westberg L et al. Interleukin-6 gene polymorphism -174G/C influences plasma lipid levels in women. Obesity (Silver Spring). 2006;14(11):1868–73.</p><p>Fernandez-Real J, Vendrell J, Richart C et al. Platelet count and Interleukin 6 Gene polymorphism in healthy subjects. BMC Med Genet. 2001;2:6. Epub 2001 Jun 1.</p><p>Marcus G, Whooley MA, Glidden D et al. Interleukin-6 and atrial fibrillation in patients with coronary artery disease: Data from the Heart and Soul Study. Am Heart J. 2008;155(2):303–9. DOI: 10.1016/j.ahj.2007.09.006. Epub 2007 Oct 25. PubMed PMID: 18215601; PubMed Central PMCID: PMC2247366.</p><p>Aker S, Bantis C, Reis P et al. Influence of interleukin-6 G-174C gene polymorphism on coronary artery disease, cardiovascular complications and mortality in dialysis patients Nephrol Dial Transplant. 2009 Sep;24(9):2847–51. DOI: 10.1093/ndt/gfp141. Epub 2009 Apr 6. PubMed PMID: 19349293.</p><p>Panoulas VF, Stavropoulos-Kalinoglou A, Metsios GS et al. Association of interleukin-6 (IL-6)-174G/C gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis: the role of obesity and smoking. Atherosclerosis. 2009 May;204(1):178–83. DOI: 10.1016/j.atherosclerosis.2008.08.036. Epub 2008 Sep 6. PubMed PMID: 18848327.</p><p>Pawlik A, Wrzesniewska J, Florczak M et al. IL-6 promoter polymorphism in patients with rheumatoid arthritis. Scand J Rheumatol. 2005;34(2):109–13. PubMed PMID: 16095005. DOI: 10.1080%2F03009740510026373.</p><p>Palomino-Morales R, Gonzalez-Juanatey C, Vazquez-Rodriguez TR et al. Interleukin-6 gene -174 promoter polymorphism is associated with endothelial dysfunction but not with disease susceptibility in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2009 Nov-Dec;27(6):964–70. PubMed PMID: 20149313.</p><p>Navab M, Hama SY, Anantharamaiah GM et al. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3. J Lipid Res. 2000;41(9):1495–508. PubMed PMID: 10974057.</p><p>Navab M, Hama SY, Cooke CJ et al. Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1. J Lipid Res. 2000;41(9):1481-94. PubMed PMID: 10974056.</p><p>Navab M, Hama-Levy S, Van Lenten BJ et al. Mildly oxidised LDL induces an increased apolipoprotein J/paraoxonase ratio. J Clin Invest. 1997;99 (8):2005–19. PubMed PMID: 9109446; PubMed Central PMCID: PMC508026.</p><p>Mackness MI, Arrol S, Durrinton PN. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett. 1991;286(1–2):152–4. PubMed PMID: 1650712. DOI: 10.1016%2F0014-5793%2891%2980962-3.</p><p>Watson AD, Navab M, Hama SY et al. Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein. J Clin Invest. 1995;95(2):774–82. DOI: 10.1172%2FJCI117726. PubMed PMID: 7860760; PubMed Central PMCID: PMC295551.</p><p>Gomaraschi M, Basilico N, Sisto F et al. High-density lipoproteins attenuate interleukin-6 production in endothelial cells exposed to proinflammatory stimuli. Biochim Biophys Acta. 2005;1736(2):136–43. PubMed PMID: 16135414.</p><p>Choi E, Sattar N. Interpreting lipid levels in the contex of high-grade inflammatory states with a focus on rheumatoid arthritis: a challenge to conventional cardiovascular risk actions. Ann Rheum Dis. 2009:68(4):460–9. DOI: 10.1136/ard.2008.101964. PubMed PMID: 19286905.</p><p>Khovidhunkit W, Kim MS, Memon RA et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host. J Lipid Res. 2004;45(7):1169–96. DOI: 10.1194%2Fjlr.R300019-JLR200. Epub 2004 Apr 21. PubMed PMID: 15102878.</p><p>Попкова ТВ, Новикова ДС, Новиков АА и др. Роль нарушений в системе транспорта холестерина крови в развитии атеросклероза при ревматоидном артрите. Научно-практическая ревматология. 2007;5:4–10. [Popkova TV, Novikova DS, Novikov AA i dr. Rol' narusheniy v sisteme transporta kholesterina krovi v razvitii ateroskleroza pri revmatoidnom artrite. Nauchno-prakticheskaya revmatologiya. 2007;5:4–10.]</p><p>Hashizume M, Yoshida H, Koike N et al. IL-6 reduces blood lipid levels via up-regulation of VLDR receptors. Arthritis Rheum. 2009;60(Suppl. 10):s11.</p><p>Woods A, Brull DJ, Humphries SE, Montgomery HE. Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6. Eur Heart J. 2000;21(19):1574–83. DOI: 10.1053%2Feuhj.1999.2207. PubMed PMID: 10988009.</p><p>Subbanagounder G, Wong JW, Lee H et al. Epoxyisoprostane and epoxycyclopentenone phospholipids regulate monocyte chemotactic protein-1 and interleukin-8 synthesis. Formation of these oxidized phospholipids in response to interleukin-1β. J Biological Chemistry. 2002;277(9):7271–81. DOI: 10.1074%2Fjbc.M107602200. Epub 2001 Dec 19. PubMed PMID: 11751881.</p><p>Klouche M, Rose-John S, Schmiedt W, Bhakdi S. Enzymatically degraded, nonoxidized LDL induces human vascular smooth muscle cell activation, foam cell transformation, and proliferation. Circulation. 2000 Apr 18;101(15):1799–805. DOI: 10.1161%2F01.CIR.101.15.1799. PubMed PMID: 10769280.</p><p>Klouche M, Bhakdi S, Hemmes M, Rose-John S. Novel path to activation of vascular smooth muscle cells: up-regulation of gp130 creates an autocrine activation loop by IL-6 and its soluble receptor. J Immunol. 1999 Oct 15; 163(8):4583–9. PubMed PMID: 10510402.</p><p>Nickenig G, Sachinidis A, Michaelson F et al. Upregulation of vascular angiotensin II receptor gene expression by Low density lipoprotein in vascular smooth muscle cells. Circulation. 1997;95(2):473–78. DOI: 10.1161%2F01.CIR.95.2.473. PubMed PMID: 9008466.</p><p>Funakoshi Y, Ichiki T, Ito K, Takeshita A. Induction of interleukin-6 expression by angiotensin II in rat vascular smooth muscle cells. Hypertension. 1999;34(1):118–25. DOI: 10.1161%2F01.HYP.34.1.118. PubMed PMID: 10406834.</p><p>Keidar S, Heinrich R, Kaplan M et al. Angiotensin II administration to atherosclerotic mice increases macrophage uptake of oxidized ldl: a possible role for interleukin-6. Arterioscler Thromb Vasc Biol. 2001;21(9):1464–9. DOI: 10.1161%2Fhq0901.095547. PubMed PMID: 11557673.</p><p>Kaplan M, Aviram M, Knopf C, Keidar S. Angiotensin II reduces macrophage cholesterol efflux: a role for the AT-1 receptor but not for the ABC1 transporter. Biochem Biophys Res Commun. 2002;290(5):1529–34. DOI: 10.1006%2Fbbrc.2002.6376. PubMed PMID: 11820795.</p><p>Насонов ЕЛ. Перспективы применения статинов в ревматологии. Русский медицинский журнал 2003;11:127–6.</p><p>[Nasonov EL. Perspektivy primeneniya statinov v revmatologii. Russkiy meditsinskiy zhurnal 2003;11:127–6.]</p><p>Gazi IF, Boumpas DT, Mikhailidis DP et al. Clustering of cardiovascular risk factors in rheumatoid arthritis: the rationale for using statins. Clin Exp Rheumatol. 2007;25(1):102–11. PubMed PMID: 17418000.</p><p>Bisoendial R, Stroes E, Kastelein J, Tak P. Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins. Nat Rev Rheumatol. 2010 Mar;6(3):157–64. DOI: 10.1038/nrrheum.2009.277. Epub 2010 Feb 9. PubMed PMID: 20142814.</p><p>Abeles AM, Pillinger M. Statins as antiinflammmatory and immunomadulatory agents. A future in rheumatologic therapy? Arthritis Rheum. 2006;54(2):393–407. DOI: 10.1002%2Fart.21521. PubMed PMID: 16447216.</p><p>Ширинский ИВ, Козлов ВА, Ширинский ВС. Использование статинов – новый подход к терапии аутоиммунных заболеваний. Вестник РАМН 2009;2:26–31. [Shirinsky IV, Kozlov VA, Shirinsky VS. The use of statins, a new approach to the treatment of autoimmune diseases. Vestnik RAMN 2009;2:26–31.]</p><p>Никитина НМ, Ребров АП. Место статинов в комплексной терапии больных ревматоидным артритом. Болезни сердца и сосудов 2009;4:58–61. [Nikitina NM, Rebrov AP. Mesto statinov v kompleksnoy terapii bol'nykh revmatoidnym artritom. Bolezni serdtsa i sosudov 2009;4:58–61.]</p><p>Jougasaki M, Ichiki T, Takenoshita Y, Setoguchi M. Statins suppress interleukin-6-induced monocyte chemo-attractant protein-1 by inhibiting Janus kinase/signal transducers and activators of transcription pathways in human vascular endothelial cells. Br J Pharmacol. 2010;159(6):1294–303. DOI: 10.1111/j.1476-5381.2009.00612.x. Epub 2010 Feb 5. PubMed PMID: 20136831; PubMed Central PMCID: PMC2848933.</p><p>Arnaud C, Burger F, Steffens S et al. Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins. Arterioscler Thromb Vasc Biol. 2005;25(6):1231–6. DOI: 10.1161%2F01.ATV.0000163840.63685.0c. Epub 2005 Mar 24. PubMed PMID: 15790934.</p><p>Park OY, Kim SH, Ahn YK et al. Statin reduces C-reactive protein and interleukin-6 in normocholesterolemic patients with acute coronary syndrome. J Chonnam Med. 2008;44:13–6. DOI: 10.4068%2Fcmj.2008.44.1.13.</p><p>Loppnow H, Zhang L, Buerke M et al. Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC cocultures. J Cell Mol Med. 2011 Apr;15(4):994-1004. DOI:10.1111/j.1582-4934.2010.01036.x. PubMed PMID: 20158569.</p><p>Hirano T, Matsuda T, Turner M et al. Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988;18(11):1797–801. DOI: 10.1002%2Feji.1830181122. PubMed PMID: 2462501.</p><p>Насонов ЕЛ. Применение тоцилизумаба (Актемры) при ревматоидном артрите. Научно-практическая ревматология. 2009;3:18–35. [Nasonov EL. Primenenie totsilizumaba (Aktemry) pri revmatoidnom artrite. Nauchno-prakticheskaya revmatologiya. 2009;3:18–35.]</p><p>Kawashiri SY, Kawakami A, Yamasaki S et al. Effects of the anti-interleukin-6 receptor antibody, tocilizumab, on serum lipid levels in patients with rheumatoid arthritis. Rheumatol Int. 2011;31(4):451–6. DOI: 10.1007/s00296-009-1303-y. Epub 2009 Dec 19. PubMed PMID: 20024554.</p><p>Nishimoto N, Miyasaka N, Yamamoto K et al. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol 2009;19(1):12–19. DOI: 10.1007/s10165-008-0125-1. Epub 2008 Nov 1. PubMed PMID: 18979150; PubMed Central PMCID: PMC2638601.</p><p>Kremer J. et al. Tocilizumab inhibits structural joint damage, improves physical function, and increases DAS28 remission rates in RA patients who respond inadequately to methotrexate: The LITHE Study. Presented on 12th June 2009 at EULAR. Fleischmann RM, Halland AM, Brzosko M et al. Tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate: LITHE study 2-year results. J Rheumatol. 2013 Feb;40(2):113–26. DOI: 10.3899/jrheum.120447. Epub 2013 Jan 15. PubMed PMID: 23322466.</p><p>Maini RN, Taylor PC, Szechinski J et al. Double-blind randomized controlled clinical trial of the interleukin 6 receptor antagonist, tocilizumab in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006;54(9):2817–29. PubMed PMID: 16947782.</p><p>McInnes I, Lee JS, Wu W, Sattar NA. Translational, Randomized, Placebo(PBO)-Controlled Study to evaluate the effects of tocilizumab (TCZ) on parameters of lipids and inflammation. Ann Rheum Dis. 2011;70(Suppl3):73.</p><p>Sattar N, Lee JS, Rowell L, McInnes I. Tocilizumab-induced alterations in lipid and apolipoprotein levels correlate with changes in clinical inflammatory markers in rheumatoid arthritis (RA). Ann Rheum Dis. 2011;70(Suppl3):588.</p><p>Jones G, Sebba A, Gu J et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010 Jan;69(1):88–96. DOI: 10.1136/ard.2008.105197. PubMed PMID: 19297346; PubMed Central PMCID: PMC3747519.</p><p>Genovese MC, Smolen JS, Emery P et al. Concomitant use of statins in tocilizumab-treated patients with rheumatoid arthritis with elevated low density lipoprotein cholesterol: analysis of five phase 3 clinical trials. Program and abstracts of the American College of Rheumatology (ACR) 2008 Annual Scientific Meeting; October 24–29, 2008; San Francisco, California. Abstract 1672.</p></div><br />


Для цитирования:


Удачкина Е.В., Новикова Д.С., Попкова Т.В., Насонов Е.Л. Роль интерлейкина 6 в развитии атеросклероза при ревматоидном артрите. Современная ревматология. 2013;7(3):25-32. https://doi.org/10.14412/1996-7012-2013-7

For citation:


Udachkina E.V., Novikova D.S., Popkova T.V., Nasonov E.L. Role of interleukin-6 in the development of atherosclerosis in rheumatoid arthritis. Modern Rheumatology Journal. 2013;7(3):25-32. (In Russ.) https://doi.org/10.14412/1996-7012-2013-7

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ISSN 1996-7012 (Print)
ISSN 2310-158X (Online)