Primary pathologic role of interleukin-6 in rheumatoid arthritis

Abstract

BACKGROUND Interleukin-6 (IL-6) is a polyfunctional cytokine that regulates a very large number of cellular activities. Its implication in acute-phase reactant production by hepatocytes is of particular interest, as is its involvement in chronic inflammatory diseases, mainly rheumatoid arthritis, Crohn’s disease, and Castleman’s disease. Transgenic mice lacking IL-6 expression were completely protected against collagen-induced arthritis, and Tumor Necrosis Factor (TNF-alpha) induces synovial cells to produce IL-6 and their proliferation. However, there is still some controversies regarding the unique proinflammatory activity of IL-6. Some studies have demonstrated that IL-6 and TNF-alpha may have an opposite effect in synovial cultured cells since IL-6 could represent a negative loop for TNF-alpha induced synovitis. However, phase III studies of rheumatoid arthritis patients treated with anti IL-6 receptor (tocilizumab) indicate an acceptable safety profile relative to the clinical benefit.
AIM OF THE STUDY In this review, we summarized the rationale and the main evidence regarding the therapeutic benefit of blocking IL-6 activity in rheumatoid arthritis.