Interleukin-6 inhibitor is the most abundant cytokines in blood and rheumatoid synovium of RA patient, and IL-6 is related do disease activities and joint destruction. IL-6 activates cells through membrane-bound receptor (mIL-6R) and soluble receptor (sIL-6R), thus induces many of local and systemic effects of this disease since this widens the number of cell types responsive to this cytokine. At joint level, IL-6 plays a key role in chronic and acute inflammation, which results in increased bone resorption, joint destruction, panus formation. Systemic effects of IL-6 include regulate acute-phase protein synthesis, hepcidin production, and stimulation of hypothalamopituitary-adrenal axis which potentially lead to anemia and fatigue. Further, IL-6 is important in B-cell maturation and therefore production of antibody. In patients with established RA, many of the articular and systemic manifestations can be explained by the effects of IL-6. This makes inhibition of the IL-6R with a monoclonal become a logicar target for treatment of RA patients.
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