General information on IL6 protein
IL-6 (interleukin 6) is a protein encoded by IL6 gene in humans. IL6 protein acts as a pro-inflammatory cytokine. Cytokines are a category of molecules that are involved in autocrine, paracrine and endocrine signaling and affect the immune system. IL6 protein also acts as an anti-inflammatory myokine. The latter are molecules produced and released by muscle cells in response to muscular contraction. Myokines too have paracrine, autocrine and endocrine effect. The role of IL6 protein as anti-inflammatory myokine is mediated through the inhibition of TNF-alpha, IL-1 as well as the activation of IL-1a and Il-10. IL6 protein levels in the plasma are increased during exercise up to 100-fold. The magnitude of IL6 plasma levels increased is determined by the combination of intensity, duration and mode of exercise. The increase occurs at the end of exercise or shortly after. During exercise, this protein acts in a hormone-like way and enhances the appearance of other cytokines.
IL6 protein is involved in the signaling pathway of both myocytes and macrophages. However, the upstream and downstream IL-6 signaling pathway is significantly different for these cell types. For macrophages and monocytes, IL6 protein induced signaling is dependent on the activation of the NFκB signaling pathway. Hence, the activation of monocytes and macrophages by IL6 signaling is followed by a pro-inflammatory response. This is not the case for IL6-induced signaling in muscle cells which is anti-inflammatory. IL6 protein muscle signaling includes Ca2+/NFAT and glycogen/p38 MAPK pathways but is independent of TNF-response or NFκB activation.
IL6 proteins are secreted by macrophages as well as adipocytes. IL6 protein is able to cross blood-brain barrier and initiate the synthesis of prostaglandin E2 (PGE2) in hypothalamus. This leads to a change of the body’s temperature setpoint. IL6 protein also increases body temperature by stimulating energy mobilization in muscle and fatty tissues. As such IL6 protein is considered to be a key mediator of fever and acute immune response.