Interleukin-6 (IL-6) is a pro-inflammatory cytokine secreted by T cells and macrophages to stimulate immune response to trauma, especially burns or other tissue damage leading to inflammation. Additionally osteoblasts to stimulate osteoclast formation. Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis. IL-6 is one of the most important mediators of fever and of the acute phase response. In the muscle and fatty tissue IL-6 stimulates energy mobilization which leads to increased body temperature. IL-6 can be secreted by [macrophage? macrophages] in response to pathogen associated molecular patterns (PAMPs) binding the Toll-like Receptor (TLR) present on an active macrophage.
IL-6 is released in response to IL-1 and TNF-b (1) The IL-6 receptor is found on many cell surfaces, including resting normal T-cells, activated normal B-cells, myeloid cell lines, hepatoma cell lines, myeloma cell lines, and on Epstein-Barr virus (EBV) modified B-cells, in which it promotes proliferation. (2)
Recently, it has been shown that IL-6 also acts as a "myokine," a cytokine produced from muscle, and is elevated in response to muscle contraction (3).
Suggested pathway of interaction leading to Secreted of IL-6 and some of its possible effects. Source
IL-6 mediates its responses through cell surface receptors that include the transmambrane protein gp130. IL-6 triggers the formation of protein complexes of gp130 and the IL-6 receptor activating the receptor. These complexes bring together the intracellular regions of gp130 and initiates the signal transduction cascade through Janus kinases (JAKs) and Signal Transducers and Activators of transcription (STATs).
IL-6 is probably the best studied of the cytokines that utilise gp130 in their signalling complexes. Other cytokines that signal through receptors containing gp130 are Interleukin-11 (IL-11), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF), oncostatin M (OSM), Kaposi's sarcoma associated herpes virus interleukin 6 like protein (KSHV-IL6). These cytokines are comonly referred to as the IL-6 like or gp130 utilising cytokines.
Drugs that Bind IL-6
Because IL-6 plays a major role in many undesired effects of the immune system, some research has been done into preventing its binding. However, it has been found somewhat more effective to bind IL-1 and TNF-b , and in this way reduce the secretion of IL-6 in the first place. One important drug in this field is the anti IL- 6 receptor antibody (MRA), used as one of new therapeutic approaches in rheumatic arthritis.
The inhibitory effect of quercetin on IL-6 production by LPS-stimulated neutrophils
Cell Mol Immunol. 2005 Dec;2(6):455-60. Liu J, Li X, Yue Y, Li J, He T, He Y.
1. Makino T, Noguchi Y, Yoshikawa T, Doi C, Nomura K. Circulating interleukin 6 concentrations and insulin resistance in patients with cancer. Br J Surg. 1998 Dec;85(12):1658-62.
2. Tosato G, Pike SE. Interferon-beta 2/interleukin 6 is a co-stimulant for human T lymphocytes. Immunol. 1988 Sep 1;141(5):1556-62.
3. Febbraio MA, Pedersen BK. Contraction-induced myokine production and release: is skeletal muscle an endocrine organ?". Exerc Sport Sci Rev 33 2005 (3): 114-9.
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