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Gene Review

Il6  -  interleukin 6

Rattus norvegicus

Synonyms: IL-6, ILg6, Ifnb2, Il-6, Interleukin-6
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Disease relevance of Il6


Psychiatry related information on Il6


High impact information on Il6


Chemical compound and disease context of Il6


Biological context of Il6


Anatomical context of Il6

  • In addition, IL-6 with dexamethasone, dexamethasone alone, and increased extracellular zinc each reversed, in decreasing potency, the deleterious effects of CCl4 on hepatocyte viability as measured by cell protein and lactate dehydrogenase activity of the medium [19].
  • Transforming growth factor beta (10 micrograms) and IL-6 (10 micrograms) coinjected intratracheally with LPS (10 micrograms) each inhibited the number of neutrophils in 6-hour bronchoalveolar lavage (BAL) specimens by approximately 50% [20].
  • IL-6 (10 ng/ml) also potentiated IL-1beta-mediated NO synthesis and inhibition of insulin release, whereas beta-nerve growth factor (NGF) (5 or 50 ng/ml) had no effect. mRNA for CNTF was expressed in rat islets and in islet cell lines [21].
  • Cytokines of the interleukin 6 (IL-6) subfamily are a group of factors produced by osteoblasts and acting through the same transducing element, membrane protein gp130 [22].
  • LIF, but not IL-6, regulates osteoprogenitor differentiation in rat calvaria cell cultures: modulation by dexamethasone [22].

Associations of Il6 with chemical compounds

  • Responses to IL-6 required the synthetic glucocorticoid hormone dexamethasone and were optimized by increased extracellular zinc [19].
  • Exogenous H(2)O(2) caused modest stimulation of TNF-alpha synthesis, did not affect the synthesis of NO or IL-6, and did not activate NF-kappaB or MAPKs [23].
  • Interleukin-6 (IL-6) alone or in combination with IL-1beta inhibits glucose-stimulated insulin release from isolated rat pancreatic islets by unknown mechanisms [21].
  • Coadministration of PPAR-gamma antagonist along with androstenediol, however, prevented the androstenediol-mediated reduction in cardiac iNOS and IL-6 expressions and abolished the improvements in cardiac function [24].
  • Gel shifts confirmed formation of nuclear factors binding to both Stat and gamma-interferon-activated sequence consensus sequences in response to NE and IL-6 [25].
  • Cotransfection of type I PKG enhanced the cGMP effect on the IL-6 promoter, whereas small interfering RNA-mediated silencing of PKG I expression prevented the cGMP effect on IL-6 mRNA expression [26].

Physical interactions of Il6

  • Additionally, IL-6 binding was also competed by CNTF, although not entirely [27].
  • The 92 kD Stat factor binding at the IL-6 RE probably also functions as a transcription factor in the cytokine-induced activation of the alpha 2M gene [28].

Regulatory relationships of Il6


Other interactions of Il6

  • Mechanisms of endotoxin-induced NO, IL-6, and TNF-alpha production in activated rat hepatic stellate cells: role of p38 MAPK [23].
  • During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion [33].
  • Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours [33].
  • CONCLUSION: The androstenediol-mediated salutary effects on cardiac function following T-H appear to be mediated at least in part via PPAR-gamma activation, which down-regulates IL-6 and iNOS gene expression in the heart [24].
  • Using retroviral luciferase reporters, we found that NE also activated both signal transducers and activators of transcription (Stat) and gamma-interferon-activated sequence-mediated transcriptional responses, with maximal effects similar to those caused by interleukin-6 (IL-6) [25].

Analytical, diagnostic and therapeutic context of Il6


  1. Regulation of CCAAT/Enhancer binding protein, interleukin-6, interleukin-6 receptor, and gp130 expression during myocardial ischemia/reperfusion. Chandrasekar, B., Mitchell, D.H., Colston, J.T., Freeman, G.L. Circulation (1999) [Pubmed]
  2. Involvement of PKC-beta in PTH, TNF-alpha, and IL-1 beta effects on IL-6 promoter in osteoblastic cells and on PTH-stimulated bone resorption. Radeff, J.M., Nagy, Z., Stern, P.H. Exp. Cell Res. (2001) [Pubmed]
  3. Prevention of neuron and oligodendrocyte degeneration by interleukin-6 (IL-6) and IL-6 receptor/IL-6 fusion protein in organotypic hippocampal slices. Pizzi, M., Sarnico, I., Boroni, F., Benarese, M., Dreano, M., Garotta, G., Valerio, A., Spano, P. Mol. Cell. Neurosci. (2004) [Pubmed]
  4. Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-alpha, macrophage inflammatory protein-2, interleukin-1 beta, and interleukin-6 but not RANTES or transforming growth factor-beta 1 mRNA expression in acute lung inflammation. Xing, Z., Jordana, M., Kirpalani, H., Driscoll, K.E., Schall, T.J., Gauldie, J. Am. J. Respir. Cell Mol. Biol. (1994) [Pubmed]
  5. Interleukin-6 and transforming growth factor-beta synergistically stimulate chondrosarcoma cell proliferation. Guerne, P.A., Lotz, M. J. Cell. Physiol. (1991) [Pubmed]
  6. Induction and regulation of interleukin-6 gene expression in rat astrocytes. Benveniste, E.N., Sparacio, S.M., Norris, J.G., Grenett, H.E., Fuller, G.M. J. Neuroimmunol. (1990) [Pubmed]
  7. Aging and glial responses to lipopolysaccharide in vitro: greater induction of IL-1 and IL-6, but smaller induction of neurotoxicity. Xie, Z., Morgan, T.E., Rozovsky, I., Finch, C.E. Exp. Neurol. (2003) [Pubmed]
  8. Interleukin-6 alters sleep of rats. Hogan, D., Morrow, J.D., Smith, E.M., Opp, M.R. J. Neuroimmunol. (2003) [Pubmed]
  9. Interleukin-6 and perioperative thermoregulation and HPA-axis activation. De Jongh, R.F., Vissers, K.C., Booij, L.H., De Jongh, K.L., Vincken, P., Meert, T.F. Cytokine (2003) [Pubmed]
  10. Short-chain ceramide regulates hepatic methionine adenosyltransferase expression. Frago, L.M., Pañeda, C., Fabregat, I., Varela-Nieto, I. J. Hepatol. (2001) [Pubmed]
  11. Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain. Trautwein, C., Caelles, C., van der Geer, P., Hunter, T., Karin, M., Chojkier, M. Nature (1993) [Pubmed]
  12. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. Villa, P., Bigini, P., Mennini, T., Agnello, D., Laragione, T., Cagnotto, A., Viviani, B., Marinovich, M., Cerami, A., Coleman, T.R., Brines, M., Ghezzi, P. J. Exp. Med. (2003) [Pubmed]
  13. Selective neutralization of prostaglandin E2 blocks inflammation, hyperalgesia, and interleukin 6 production in vivo. Portanova, J.P., Zhang, Y., Anderson, G.D., Hauser, S.D., Masferrer, J.L., Seibert, K., Gregory, S.A., Isakson, P.C. J. Exp. Med. (1996) [Pubmed]
  14. Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival. Maeda, Y., Matsumoto, M., Hori, O., Kuwabara, K., Ogawa, S., Yan, S.D., Ohtsuki, T., Kinoshita, T., Kamada, T., Stern, D.M. J. Exp. Med. (1994) [Pubmed]
  15. The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10. Dahle, M.K., Øverland, G., Myhre, A.E., Stuestøl, J.F., Hartung, T., Krohn, C.D., Mathiesen, Ø., Wang, J.E., Aasen, A.O. Infect. Immun. (2004) [Pubmed]
  16. Somatostatin and gamma-aminobutyric acid inhibit interleukin-1 beta-stimulated release of interleukin-6 from rat C6 glioma cells. Spangelo, B.L., Horrell, S., Goodwin, A.L., Shroff, S., Jarvis, W.D. Neuroimmunomodulation (2004) [Pubmed]
  17. Increased expression of IL-6 and LIF in the hypertrophied left ventricle of TGR(mRen2)27 and SHR rats. Kurdi, M., Randon, J., Cerutti, C., Bricca, G. Mol. Cell. Biochem. (2005) [Pubmed]
  18. Desflurane differentially affects the release of proinflammatory cytokines in plasma and bronchoalveolar fluid of endotoxemic rats. Boost, K.A., Hofstetter, C., Flondor, M., Betz, C., Homann, M., Pfeilschifter, J., Muehl, H., Zwissler, B. Int. J. Mol. Med. (2006) [Pubmed]
  19. Interleukin 6 regulates metallothionein gene expression and zinc metabolism in hepatocyte monolayer cultures. Schroeder, J.J., Cousins, R.J. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  20. Intratracheal injection of endotoxin and cytokines. II. Interleukin-6 and transforming growth factor beta inhibit acute inflammation. Ulich, T.R., Yin, S., Guo, K., Yi, E.S., Remick, D., del Castillo, J. Am. J. Pathol. (1991) [Pubmed]
  21. Ciliary neurotrophic factor potentiates the beta-cell inhibitory effect of IL-1beta in rat pancreatic islets associated with increased nitric oxide synthesis and increased expression of inducible nitric oxide synthase. Wadt, K.A., Larsen, C.M., Andersen, H.U., Nielsen, K., Karlsen, A.E., Mandrup-Poulsen, T. Diabetes (1998) [Pubmed]
  22. LIF, but not IL-6, regulates osteoprogenitor differentiation in rat calvaria cell cultures: modulation by dexamethasone. Malaval, L., Gupta, A.K., Liu, F., Delmas, P.D., Aubin, J.E. J. Bone Miner. Res. (1998) [Pubmed]
  23. Mechanisms of endotoxin-induced NO, IL-6, and TNF-alpha production in activated rat hepatic stellate cells: role of p38 MAPK. Thirunavukkarasu, C., Watkins, S.C., Gandhi, C.R. Hepatology (2006) [Pubmed]
  24. A role of PPAR-gamma in androstenediol-mediated salutary effects on cardiac function following trauma-hemorrhage. Shimizu, T., Szalay, L., Hsieh, Y.C., Suzuki, T., Choudhry, M.A., Bland, K.I., Chaudry, I.H. Ann. Surg. (2006) [Pubmed]
  25. Activation of signal transducers and activators of transcription by alpha(1A)-adrenergic receptor stimulation in PC12 cells. Zhong, H., Murphy, T.J., Minneman, K.P. Mol. Pharmacol. (2000) [Pubmed]
  26. Guanosine 3',5'-cyclic monophosphate (cGMP)/cGMP-dependent protein kinase induce interleukin-6 transcription in osteoblasts. Broderick, K.E., Zhang, T., Rangaswami, H., Zeng, Y., Zhao, X., Boss, G.R., Pilz, R.B. Mol. Endocrinol. (2007) [Pubmed]
  27. Ciliary neurotrophic factor regulates fibrinogen gene expression in hepatocytes by binding to the interleukin-6 receptor. Nesbitt, J.E., Fuentes, N.L., Fuller, G.M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  28. Isolation of two interleukin-6 response element binding proteins from acute phase rat livers. Ripperger, J., Fritz, S., Richter, K., Dreier, B., Schneider, K., Löchner, K., Marschalek, R., Hocke, G., Lottspeich, F., Fey, G.H. Ann. N. Y. Acad. Sci. (1995) [Pubmed]
  29. Inhibition by interleukin-1 beta and tumor necrosis factor-alpha of the insulin-like growth factor I messenger ribonucleic acid response to growth hormone in rat hepatocyte primary culture. Thissen, J.P., Verniers, J. Endocrinology (1997) [Pubmed]
  30. Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons. Akaneya, Y., Takahashi, M., Hatanaka, H. Exp. Neurol. (1995) [Pubmed]
  31. Interleukin-6 increases rat metalloproteinase-13 gene expression through Janus kinase-2-mediated inhibition of serine/threonine phosphatase-2A. de la Torre, P., Díaz-Sanjuán, T., García-Ruiz, I., Esteban, E., Canga, F., Muñoz-Yagüe, T., Solís-Herruzo, J.A. Cell. Signal. (2005) [Pubmed]
  32. IL-6 up-regulates CNTF mRNA expression and enhances neurite regeneration. Shuto, T., Horie, H., Hikawa, N., Sango, K., Tokashiki, A., Murata, H., Yamamoto, I., Ishikawa, Y. Neuroreport (2001) [Pubmed]
  33. Cytokine mRNA expression in postischemic/reperfused myocardium. Herskowitz, A., Choi, S., Ansari, A.A., Wesselingh, S. Am. J. Pathol. (1995) [Pubmed]
  34. The expression of interleukin-6 (IL-6), IL-6 receptor, and gp130-kilodalton glycoprotein in the rat decidua and a decidual cell line: regulation by 17beta-estradiol and prolactin. Deb, S., Tessier, C., Prigent-Tessier, A., Barkai, U., Ferguson-Gottschall, S., Srivastava, R.K., Faliszek, J., Gibori, G. Endocrinology (1999) [Pubmed]
  35. Comparative evaluation of cytokine profiles and reactive gliosis supports a critical role for interleukin-6 in neuron-glia signaling during regeneration. Streit, W.J., Hurley, S.D., McGraw, T.S., Semple-Rowland, S.L. J. Neurosci. Res. (2000) [Pubmed]
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