The objective review is to inspect the involvement of Interleukin-6 (IL-6) in rheumatoid arthritis (RA) and to highlight the role of IL-6 and its variants in the pathogenesis of RA and response to anti-IL-6 agents. Several genetic and environmental risk factors and infectious agents contributed to the development of RA. Interleukin-6 is engaged in self-targeted immunity by modifying the equilibrium between T regulatory (T-reg) and T helper-17 (Th-17) cells. The evidences reported that IL-6 parti