Interleukin 6 (IL-6)
Overview
Interleukin-6 (IL-6) is a member of the pro-inflammatory cytokine family1.
IL-6 functions to induce the expression multiple types of proteins that are responsible for acute inflammation, and plays an important role in the proliferation and differentiation of cells in humans1
- Interleukin-6: A Masterplayer in the Cytokine Network1
Structure
- IL-6 is a pleiotropic cytokine1
Production
IL-6 is primarily produced by Monocytes and Macrophages1. Other cells also generate IL-6, such as T cells, B cells, hepatocytes, endothelial cells, fibroblasts, keratinocytes, mesangial cells, and adipocytes, as well as several tumor cells1
Stimulation
Function
During inflammatory conditions and infections, IL-6 production is induced via stimulation of cells by IL-1 or TNF-α or through stimulation of Toll-like receptors after binding of pathogenic patterns of microbes1.
IL-6 can influence both immune and physiological processes
acute phase protein generation (e.g., C-reactive protein (CRP), hepcidin, etc.), inflammation, antigen-specific immune responses, hematopoiesis, apoptosis, differentiation, and cellular metabolism [4, 6, 7].
Immunopathogenic Functions
“Many studies have described the immunopathogenic function of IL-6 in regulating tumor growth, angiogenesis, apoptosis, metastasis, and therapeutic resistance [1012]. There are various signaling pathways for IL-6, and many of the molecules involved are therapeutic targets to alter IL-6 expression and function in non-malignant diseases and cancer.”1
Mediation
“IL-6 signaling is mediated by building a complex of IL-6, the transmembrane IL-6 receptor (mIL-6R) or with soluble forms of IL-6R (sIL-6R), and the signal-transducing subunit molecule gp130”1
Dysfunction
Dysfunction in IL-6 regulation, resulint gin increased IL-6 expression has been associated with the pathogenesis of several disorders, including chronic inflammatory diseases, autoimmune diseases, and tumor development1.
IL-6 Receptors
“In the classic signal cascade, only cells which express the transmembrane 80-kDa α-receptor subunit IL-6R (mIL-6R, CD126) respond to IL-6. The monomeric complex of IL-6 and mIL-6R associates with a ubiquitously expressed 130-kDa β-receptor subunit receptor (gp130, CD130) and results in gp130 dimerization. gp130 is a binding and signal transducer molecule for several members of the IL-6 family (e.g., oncostatin M, IL-11, ciliary neurotrophic factor, cardiotrophin-1, leukemia inhibitory factor, cardiotrophin-like cytokine, IL-27, and IL35) [8, 13]. However, there are also soluble forms with can build a complex with IL-6 and gp130. One soluble form of IL-6R (sIL-6R) can be released by cleavage of the membrane-bound IL-6R by ADAM 10/17 (a disintegrin and metalloprotease domain-containing protein) [14], and another form of sIL-6R through alternative RNA splicing [14]. In addition, a soluble form of gp130 (sgp130) exists, generated by alternative splicing. The mechanisms by which sgp130 influences the signaling pathways of other cytokines than IL-6 have not been elucidated yet.”