2015, Number 1
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ABSTRACTRheumatoid arthritis (RA) is a chronic degenerative disease that causes joint inflammation, cartilage destruction and systemic manifestations such as anemia, fatigue and osteoporosis. IL-6 plays a major role in the pathogenesis of RA; this interleukin is easily found in the sinovial fluid and causes local and systemic effects. IL-6 is activated by its receptors: IL-6R, predominantly in the hepatocyte, and sIL-6R (soluble interleukine-6 receptor), where IL-6 binds and homodimerizes with glycoprotein 130 subunit and induces signal transduction. The presence of vascular endothelial growth factor (VEGT) contributes to the formation of pannus. High levels of IL-6 cause major synthesis of acute-phase proteins (like PCR), stimulate the production of hepcidin, develop fatigue through the stimulation of the hypothalamo-pituitary-adrenal axis, and promote osteoporosis, dyslipidemia and cardiovascular risk.
Hashizume M, Mihara M. The roles of interleukin-6 in the pathogenesis of rheumatoid arthritis. Arthritis. 2011; 2011: 765624.
Pelaez-Ballestas I, Sanin LH, Moreno-Montoya J, Alvarez-Nemegyei J, Burgos-Vargas R, Garza-Elizondo M et al. Epidemiology of the rheumatic diseases in Mexico. A study of 5 regions based on the COPCORD methodology. J Rheumatol Suppl. 2011; 86: 3-8.
Gonzalez A, Maradit KH, Crowson CS, Nicola PJ, Davis JM 3rd, Therneau TM et al. The widening mortality gap between rheumatoid arthritis patients and the general population. Arthritis Rheum. 2007; 56 (11): 3583-3587.
Chung SJ, Kwon YJ, Park MC, Park YB, Lee SK. The correlation between increased serum concentrations of interleukin-6 family cytokines and disease activity in rheumatoid arthritis patients. Yonsei Med J. 2011; 52 (1): 113-120.
Heinrich PC, Behrmann I, Haan S, Hermanns HM, Muller-Newen G, Schaper F. Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 2003; 374 (Pt 1): 1-20.
Robak T, Gladalska A, Stepien H, Robak E. Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. Mediators Inflamm. 1998; 7 (5): 347-353.
McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011; 365 (23): 2205-2219.
Park JY, Pillinger MH. Interleukin-6 in the pathogenesis of rheumatoid arthritis. Bulletin of the NYU hospital for joint diseases. 2007; 65 Suppl 1: S4-10.
Srirangan S, Choy EH. The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2010; 2 (5): 247-256.
Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999; 103 (9): 1345-1352.
Lee Y, Awasthi A, Yosef N, Quintana FJ, Xiao S, Peters A et al. Induction and molecular signature of pathogenic T(H)17 cells. Nat Immunol. 2012; 13 (10): 991-999.
Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001; 344 (12): 907-916.
Ballara S, Taylor PC, Reusch P, Marme D, Feldmann M, Maini RN et al. Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum. 2001; 44 (9): 2055-2064.
Sabeh F, Fox D, Weiss SJ. Membrane-type I matrix metalloproteinase-dependent regulation of rheumatoid arthritis synoviocyte function. J Immunol. 2010; 184 (11): 6396-6406.
Cronstein BN. Interleukin-6 –a key mediator of systemic and local symptoms in rheumatoid arthritis. Bull NYU Hospital Jt Dis. 2007; 65 Suppl 1: S11-S5.
Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology. 2010; 49 (1): 15-24.
Su D, Li Z, Li X, Chen Y, Zhang Y, Ding D et al. Association between serum interleukin-6 concentration and mortality in patients with coronary artery disease. Mediators Inflamm. 2013; 2013: 726178.
Chung CP, Oeser A, Raggi P, Sokka T, Pincus T, Solus JF et al. Lipoprotein subclasses determined by nuclear magnetic resonance spectroscopy and coronary atherosclerosis in patients with rheumatoid arthritis. J Rheumatol. 2010; 37 (8): 1633-1638.