Interleukin 6 (interferon, beta 2)
|PDB rendering based on 1ALU.|
|Available structures:, , ,|
|RNA expression pattern|
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. In terms of host response to a foreign pathogen, IL-6 has been shown, in mice, to be required for resistance against the bacterium, Streptococcus pneumoniae. IL-6 is also a "myokine," a cytokine produced from muscle, and is elevated in response to muscle contraction. Additionally, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine.
Functions of IL-6
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 specific microbial molecules, referred to as pathogen associated molecular patterns (PAMPs). These PAMPs bind to highly important detection molecules of the innate immune system, called Toll-like receptors (TLRs), that are present on the cell surface (or in intracellular compartments) which induce intracellular signaling cascades that give rise to inflammatory cytokine production. IL-6 is also essential for hybridoma growth and is found in many supplemental cloning media such as briclone. Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis.
The IL-6 receptor
IL-6 signals through a cell-surface type I cytokine receptor complex consisting of the ligand-binding IL-6Rα chain (CD126), and the signal-transducing component gp130 (also called CD130). CD130 is the common signal transducer for several cytokines including leukemia inhibitory factor(LIF), ciliary neurotropic factor, oncostatin M, IL-11 and cardiotrophin-1, and is almost ubiquitously expressed in most tissues. In contrast, the expression of CD126 is restricted to certain tissues. As IL-6 interacts with its receptor, it triggers the gp130 and IL-6R proteins to form a complex, thus activating the receptor. These complexes bring together the intracellular regions of gp130 to initiate a signal transduction cascade through certain transcription factors, Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs).
IL-6 is probably the best studied of the cytokines that use gp130 in their signalling complexes. Other cytokines that signal through receptors containing gp130 are Interleukin 11 (IL-11), Interleukin 27 (IL-27), 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 commonly referred to as the IL-6 like or gp130 utilising cytokines.
In addition to the membrane-bound receptor, a soluble form of IL-6R (sIL-6R) has been purified from human serum and urine. Many neuronal cells are unresponsive to stimulation by IL-6 alone, but differentiation and survival of neuronal cells can be mediated through the action of sIL-6R. The sIL-6R/IL-6 complex can stimulate neurites outgrowth promote survival of neurons, hence may be important in nerve regeneration through remyelination.
- ↑ van der Poll T, Keogh CV, Guirao X, Buurman WA, Kopf M, Lowry SF (1997). "Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia". J Infect Dis 176 (2): 439-44. PMID 9237710.
- ↑ Febbraio MA, Pedersen BK (2005). "Contraction-induced myokine production and release: is skeletal muscle an endocrine organ?". Exerc Sport Sci Rev 33 (3): 114-9. PMID 16006818.
- ↑ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 family of cytokines and gp130". Blood 86: 1243-1254.
- De Kloet ER, Oitzl MS, Schöbitz B (1994). "Cytokines and the brain corticosteroid receptor balance: relevance to pathophysiology of neuroendocrine-immune communication.". Psychoneuroendocrinology 19 (2): 121-34. PMID 8190832.
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- Berger FG (2005). "The interleukin-6 gene: a susceptibility factor that may contribute to racial and ethnic disparities in breast cancer mortality.". Breast Cancer Res. Treat. 88 (3): 281-5. doi:10.1007/s10549-004-0726-0. PMID 15609131.
- Stenvinkel P, Ketteler M, Johnson RJ, et al. (2005). "IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia--the good, the bad, and the ugly.". Kidney Int. 67 (4): 1216-33. doi:10.1111/j.1523-1755.2005.00200.x. PMID 15780075.
- Vgontzas AN, Bixler EO, Lin HM, et al. (2005). "IL-6 and its circadian secretion in humans.". Neuroimmunomodulation 12 (3): 131-40. doi:10.1159/000084844. PMID 15905620.
- Jones SA (2005). "Directing transition from innate to acquired immunity: defining a role for IL-6.". J. Immunol. 175 (6): 3463-8. PMID 16148087.
- Kristiansen OP, Mandrup-Poulsen T (2006). "Interleukin-6 and diabetes: the good, the bad, or the indifferent?". Diabetes 54 Suppl 2: S114-24. PMID 16306329.
- Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines.". Mini reviews in medicinal chemistry 5 (12): 1093-101. PMID 16375755.
- Mastorakos G, Ilias I (2007). "Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress.". Ann. N. Y. Acad. Sci. 1088: 373-81. doi:10.1196/annals.1366.021. PMID 17192581.
- Dubiński A, Zdrojewicz Z (2007). "[The role of interleukin-6 in development and progression of atherosclerosis]". Pol. Merkur. Lekarski 22 (130): 291-4. PMID 17684929.
|IL-1 superfamily||IL-1 (IL-1Ra) - IL-18 - IL-33|
|IL-6 like/gp130 utilizing||IL-6 - IL-11 - IL-27 - IL-30 - IL-31|
|IL-10 family||IL-10 - IL-19 - IL-20 - IL-22 - IL-24 - IL-26|
|Interferon type III||IL-28 - IL-29|
|Common γ-chain family||IL-2/IL-15 - IL-3 - IL-4 - IL-7 - IL-9 - IL-13 - IL-21|
|IL-12 family||IL-12 - IL-23 - IL-27 - IL-35|
|Other||IL-5 - IL-8 - IL-14 - IL-16 - IL-17/IL-25 (A) - IL-32|
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