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DescriptionInterleukin-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 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-6Because 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. AbstractsPathology of fatal human infection associated with avian influenza A H5N1 virusJ Med Virol. 2001 Mar;63(3):242-6 To KF, Chan PK, Chan KF, Lee WK, Lam WY, Wong KF, Tang NL, Tsang DN, Sung RY, Buckley TA, Tam JS, Cheng AF.
The inhibitory effect of quercetin on IL-6 production by LPS-stimulated neutrophilsCell Mol Immunol. 2005 Dec;2(6):455-60. Liu J, Li X, Yue Y, Li J, He T, He Y.
Tanshinone IIA from Salvia miltiorrhiza inhibits inducible NO synthase, TNF-alpha, IL-1beta and IL-6Planta Med. 2003 Nov;69(11):1057-9. Jang SI, Jeong SI, Kim KJ, Kim HJ, Yu HH, Park R, Kim HM, You YO. The inhibitory effects of tanshinone IIA, a diterpene isolated from Salvia miltiorrhiza root, on the production of nitric oxide (NO), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and the expression of inducible nitric oxide synthase (iNOS) were investigated in activated RAW 264.7 cells. This compound markedly inhibited the production of NO, IL-1beta and TNF-alpha, and suppressed the expression of iNOS in a dose-dependent manner. These results suggest that the traditional use of S. miltiorrhiza as an anti-inflammatory herbal medicine may be explained, in part, by the inhibition of NO, IL-1beta, IL-6 and TNF-alpha production, and expression of iNOS. LinksAttribution
References1. 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. |