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Gene Review

IL6ST  -  interleukin 6 signal transducer (gp130,...

Macaca mulatta

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Disease relevance of IL-6

  • These data support the hypothesis that cytokines such as IL-6 are important amplification molecules for CNS inflammation in Lyme neuroborreliosis [1].
  • However, among rapid progressors, the eight animals with SIV encephalitis had a unique cytokine profile (increased IL-2, IL-6, and IFN-gamma) that was associated with higher viral loads [2].
  • Recall responses to rotavirus by CD4(+) and CD8(+) T lymphocytes were associated with accumulation of intracellular IL-6 and gamma interferon [3].
  • Following intravenous inoculation of pig-tailed macaques with SIV-PBj14, acute disease developed and was characterized by high levels of plasma viremia, p27gag antigenemia, tumor necrosis factor alpha, and interleukin-6 (IL-6) [4].
  • Rhesus monkeys were treated s.c. with recombinant human (rh) IL-6 at 3 and 30 micrograms/kg body weight/day for 11 days, followed by the administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) at 5.5 micrograms/kg/day for 5 days [5].

Psychiatry related information on IL-6


High impact information on IL-6

  • A large fraction (> 30%) of single-cell/well-sorted CD34bright/RhLA-DRdull cells formed multilineage colonies after 2 to 4 weeks of stimulation with IL-3, GM-CSF, Kit ligand, and IL-6 [8].
  • We conclude that IL-6 significantly alters the process of megakaryocyte maturation and thrombocytopoiesis, and that these effects, at least in the doses of IL-6 administered, should not be equated with the physiologic mechanisms operative during accelerated platelet production [9].
  • Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in mice and primates [9].
  • Cytokine gene expression (interleukin-1beta [IL-1beta], IL-2, IL-6, IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and viral loads were evaluated by semiquantitative reverse transcription-PCR in lymph nodes of 5 control animals and 28 animals infected with SIVmac251 at the terminal stages of AIDS [2].
  • Elevated levels of IL-6 cDNA and, to a lesser extent, interferon gamma were detected in three of three nonhuman primates with persistent infection with B burgdorferi, whereas the brains of three uninfected animals and undetectable levels of gene expression of these cytokines [1].

Biological context of IL-6

  • In humans and nonhuman primates, the in vivo administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) consistently results in marked increase of megakaryocyte ploidy and size similar to that observed with interleukin-6 (IL-6) [10].
  • Cerebrospinal fluid (CSF) and blood levels of interleukin-6 (IL-6) were measured, as well as cortisol levels and body temperature [11].
  • In the present study, the likely involvement of inflammatory cytokines, namely, leukemia inhibitory factor (LIF), interleukins 1 alpha and 1 beta (IL-1alpha and IL-1beta) and IL-6 at the primary implantation site of the rhesus monkey was examined immunocytochemically during lacunar (n=6) and villous (n=8) stages of gestation [12].
  • The Tibetan macaque IFN-gamma and IL-6 cDNAs were found to be 498 and 639bp in length, with open reading frames encoding 165 and 212 amino acids, respectively [13].
  • Homology analyses indicated that the identity levels of nucleotide and deduced amino acid sequences of IFN-gamma among primates ranged from 93.4 to 99.2%, and 87.3 to 99.4%, respectively, and that of IL-6 ranged from 92.6 to 99.8%, and 85.4 to 99.5%, respectively [13].

Anatomical context of IL-6


Associations of IL-6 with chemical compounds


Other interactions of IL-6

  • For both SIVmac239 and its nef-deleted derivative, strong expression was observed as early as 7 days postinfection for interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor alpha, gamma interferon, and IL-13 [19].

Analytical, diagnostic and therapeutic context of IL-6


  1. Interleukin-6 is expressed at high levels in the CNS in Lyme neuroborreliosis. Pachner, A.R., Amemiya, K., Delaney, E., O'Neill, T., Hughes, C.A., Zhang, W.F. Neurology (1997) [Pubmed]
  2. Macaques with rapid disease progression and simian immunodeficiency virus encephalitis have a unique cytokine profile in peripheral lymphoid tissues. Orandle, M.S., Williams, K.C., MacLean, A.G., Westmoreland, S.V., Lackner, A.A. J. Virol. (2001) [Pubmed]
  3. Defining T-cell-mediated immune responses in rotavirus-infected juvenile rhesus macaques. Sestak, K., McNeal, M.M., Choi, A., Cole, M.J., Ramesh, G., Alvarez, X., Aye, P.P., Bohm, R.P., Mohamadzadeh, M., Ward, R.L. J. Virol. (2004) [Pubmed]
  4. Immune activation and viral burden in acute disease induced by simian immunodeficiency virus SIVsmmPBj14: correlation between in vitro and in vivo events. Schwiebert, R., Fultz, P.N. J. Virol. (1994) [Pubmed]
  5. Recombinant human interleukin 6 is a potent inducer of the acute phase response and elevates the blood platelets in nonhuman primates. Mayer, P., Geissler, K., Valent, P., Ceska, M., Bettelheim, P., Liehl, E. Exp. Hematol. (1991) [Pubmed]
  6. Interleukin-1 beta differentially affects interleukin-6 and soluble interleukin-6 receptor in the blood and central nervous system of the monkey. Reyes, T.M., Coe, C.L. J. Neuroimmunol. (1996) [Pubmed]
  7. Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. Ershler, W.B., Sun, W.H., Binkley, N., Gravenstein, S., Volk, M.J., Kamoske, G., Klopp, R.G., Roecker, E.B., Daynes, R.A., Weindruch, R. Lymphokine Cytokine Res. (1993) [Pubmed]
  8. Differential expression of receptors for interleukin-3 on subsets of CD34-expressing hematopoietic cells of rhesus monkeys. Wognum, A.W., Visser, T.P., de Jong, M.O., Egeland, T., Wagemaker, G. Blood (1995) [Pubmed]
  9. Effects of human interleukin-6 on megakaryocyte development and thrombocytopoiesis in primates. Stahl, C.P., Zucker-Franklin, D., Evatt, B.L., Winton, E.F. Blood (1991) [Pubmed]
  10. Effects of recombinant human granulocyte-macrophage colony-stimulating factor on platelet survival and activation using a nonhuman primate model. Tomer, A., Stahl, C.P., McClure, H.M., Anderson, D.C., Myers, L.A., Liehl, E., Winton, E.F. Exp. Hematol. (1993) [Pubmed]
  11. Prenatal manipulations reduce the proinflammatory response to a cytokine challenge in juvenile monkeys. Reyes, T.M., Coe, C.L. Brain Res. (1997) [Pubmed]
  12. Immunohistochemical localization of leukemia inhibitory factor, interleukins 1 and 6 at the primary implantation site in the rhesus monkey. Sengupta, J., Dhawan, L., Ghosh, D. Cytokine (2003) [Pubmed]
  13. Molecular cloning and sequence analysis of interferon-gamma and interleukin-6 from Tibetan macaque (Macaca thibetana). Wei, K., Liang, X., Zou, F., Yin, H., Yue, B. Vet. Immunol. Immunopathol. (2006) [Pubmed]
  14. Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels. van Gils, F.C., van Teeffelen, M.E., Neelis, K.J., Hendrikx, J., Burger, H., van Leen, R.W., Knol, E., Wagemaker, G., Wognum, A.W. Blood (1995) [Pubmed]
  15. Borrelia burgdorferi stimulates in vitro a selective expansion of CD3-CD4-CD8- (triple negative) autoreactive cells in naive rhesus monkey lymphocytes. Ganapamo, F., Dennis, V.A., Philipp, M.T. J. Infect. Dis. (2001) [Pubmed]
  16. Inflammatory cytokine mRNA expression during early and persistent Helicobacter pylori infection in nonhuman primates. Harris, P.R., Smythies, L.E., Smith, P.D., Dubois, A. J. Infect. Dis. (2000) [Pubmed]
  17. Cytokine responses in young and old rhesus monkeys: effect of caloric restriction. Mascarucci, P., Taub, D., Saccani, S., Paloma, M.A., Dawson, H., Roth, G.S., Lane, M.A., Ingram, D.K. J. Interferon Cytokine Res. (2002) [Pubmed]
  18. Interleukin-6 causes hypocholesterolemia in middle-aged and old rhesus monkeys. Ettinger, W.H., Sun, W.H., Binkley, N., Kouba, E., Ershler, W. J. Gerontol. A Biol. Sci. Med. Sci. (1995) [Pubmed]
  19. Early cytokine and chemokine gene expression in lymph nodes of macaques infected with simian immunodeficiency virus is predictive of disease outcome and vaccine efficacy. Zou, W., Lackner, A.A., Simon, M., Durand-Gasselin, I., Galanaud, P., Desrosiers, R.C., Emilie, D. J. Virol. (1997) [Pubmed]
  20. Association of interleukin-6 in the pathogenesis of acutely fatal SIVsmm/PBj-14 in pigtailed macaques. Birx, D.L., Lewis, M.G., Vahey, M., Tencer, K., Zack, P.M., Brown, C.R., Jahrling, P.B., Tosato, G., Burke, D., Redfield, R. AIDS Res. Hum. Retroviruses (1993) [Pubmed]
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