Hall of fame among pro-inflammatory cytokines: Interleukin-6 gene and its transcriptional regulation mechanisms

Pro-inflammatory cytokines that are generated by immune system cells and mediate many kinds of immune responses are kinds of endogenous polypeptides. They are also the effectors of the autoimmune system. It is generally accepted that interleukin (IL)-4, IL-6, IL-9, IL-17, and tumor necrosis factor-a are pro-inflammatory cytokines; however, IL-6 becomes a protagonist among them since it predominately induces pro-inflammatory signaling and regulates massive cellular processes. It has been ascertained that IL-6 is associated with a large number of diseases with inflammatory background, such as anemia of chronic diseases, angiogenesis acute-phase response, bone metabolism, cartilage metabolism, and multiple cancers. Despite great progress in the relative field, the targeted regulation of IL-6 response for therapeutic benefits remains incompletely to be understood. Therefore, it is conceivable that understanding mechanisms of IL-6 from the perspective of gene regulation can better facilitate to determine the pathogenesis of the disease, providing more solid scientific basis for clinical treatment translation. In this review, we summarize the candidate genes that have been implicated in clinical target therapy from the perspective of gene transcription regulation.