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Gene Review

IL6  -  interleukin 6

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Disease relevance of IL6

  • IL-6 signaling is activated during human chronic atrophic gastritis with Helicobacter pylori infection, and aberrant Stat3 signaling activation gives rise to mouse gastric tumors [1].
  • Delayed-type hypersensitivity (DTH) reaction, serum levels of interleukin-6 (IL-6) and anti-proteoglycan IgG titres were significantly reduced in STAT-1 decoy ODN-treated mice, whereas mBSA, collagen type I and type II specific immunoglobulins were not significantly affected [2].
  • In fact, stimulation with M. avium subsp. paratuberculosis tended to reduce the differential expression observed in infected and uninfected cows for genes encoding IFN-gamma, IL-1alpha, and IL-6 [3].
  • Several strains of the closely related Mycobacterium avium, and the unrelated saprophyte, Mycobacterium phlei, had somewhat less ability to stimulate TNF-alpha and IL-6 mRNA expression [4].
  • The cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have been associated with granuloma formation and wasting in other disease syndromes [4].

High impact information on IL6

  • METHODS: Biotinylated antibodies against alpha-fetoprotein (AFP), interleukin-6 (IL-6), and carcinoembryonic antigen [(CEA); 0.1 g/L each in 15 mmol/L phosphate-buffered saline (PBS) containing 0.1 mL/L Tween 20] were attached to a microcolumn packed with streptavidin-coated particles [5].
  • Murine bone marrow-derived dendritic cells were activated to secrete interleukin-6 (IL-6), IL-12, and tumor necrosis factor upon exposure to antigen-free TPL liposomes [6].
  • Although the activity of phosphatidylinositol dimannoside was little influenced by palmitoylation of mannose at C-6, a further palmitoylation at inositol C-3 diminished the induction levels of IL-6 and IL-12 [6].
  • Suboptimal doses of IL17 synergised potently with TNFalpha, IL1, OSM, and IL6 to promote collagen degradation [7].
  • IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage [8].

Chemical compound and disease context of IL6


Biological context of IL6


Anatomical context of IL6

  • Therefore, in the present study we determined if TMA and TMA conjugated to serum albumin induced the production of the macrophage mediators nitric oxide (NO), tumour necrosis factor (TNF), and interleukin 6 (IL-6) in vitro using the rat AM cell line NR8383 and primary AMs derived from TMA-sensitized and naïve Brown Norway rats [13].
  • IL6-induced WNT5A activates canonical WNT signaling for autocrine proliferation of human synovial fibroblasts in rheumatoid arthritis [1].
  • Thus, it appears that less differentiated granulosa cells (small follicles) are more sensitive to IL-6 than are highly differentiated granulosa cells (large follicles) [10].
  • We have investigated the involvement of interleukin 6 (IL-6), a growth-regulatory molecule for vascular smooth muscle cells (SMC), in the development of atherosclerotic lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits [14].
  • BBEC pre-incubated with IL-6 for 4 h also showed an increase in adhesion of lymphocytes, and cells pretreated with 100 ng/ml IL-6 showed a 3-fold increase in lymphocyte adherence [15].

Associations of IL6 with chemical compounds

  • EGCG and catechin had no significant effects in primary WBC on the expression pattern of the proinflammatory cytokines IL1beta and IL6 and on the expression of the housekeeping genes GAPDH and histon H3 [16].
  • In comparison, all doses of IL-6 inhibited (p < 0.05) FSH-induced estradiol production in cultures of cells from small follicles; maximal inhibition was achieved (75% decrease) with > or = 10 ng/ml [10].
  • To investigate the mechanism of the suppression induced by IL-6, we studied its effect upon PGI2 synthesizing enzymes [17].
  • The effect of interleukin 6 (IL-6) upon arachidonic acid (AA) metabolism was studied in cultured bovine vascular endothelial cells (BVECs) [17].
  • IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin [18].

Other interactions of IL6

  • Increases in transcripts for the IL6 (29 and 34 dpi) and IL10 (21, 25, and 29 dpi) genes were detected that were higher in the Boran compared with N'Dama [19].
  • STAT and MAPK pathways play a crucial role in IL-6/sIL-6R modulation of these enzymes, suggesting that new strategies in the treatment of osteoarticular diseases might target these transduction cascades [20].

Analytical, diagnostic and therapeutic context of IL6

  • Using RT-PCR techniques we have previously detected the aberrant expression of FGF4, FGFr2 and IL6 in a significant proportion of bovine granulosa cell-derived nuclear transfer embryos, which correlated with a limited developmental potential in vivo [21].
  • These findings support the premise that IL-6 is an important autocrine and/or paracrine regulator of SMC proliferation and of pathogenesis of atherosclerosis in this animal model [14].
  • In the present study, bovine articular cartilage explants were maintained in a model organ culture system in the presence or absence of IL-1alpha or TNF-alpha, and under co-stimulation with or without IL-6 and/or sIL-6R [8].
  • In in situ hybridization analysis, quite low levels of IL-6 mRNA were expressed in 'quiescent' SMC cultured from WHHL rabbits; however, high levels of IL-6 mRNA were induced in SMC exposed to 10% fetal bovine serum (FBS), suggesting that growth-stimulated SMC themselves can synthesize IL-6 [14].
  • The release of IL-1 and IL-6 by EC was measured by enzyme-linked immunosorbent assay [22].


  1. STAT3-induced WNT5A signaling loop in embryonic stem cells, adult normal tissues, chronic persistent inflammation, rheumatoid arthritis and cancer (Review). Katoh, M., Katoh, M. Int. J. Mol. Med. (2007) [Pubmed]
  2. Attenuation of murine antigen-induced arthritis by treatment with a decoy oligodeoxynucleotide inhibiting signal transducer and activator of transcription-1 (STAT-1). H??ckel, M., Schurigt, U., Wagner, A.H., St??ckigt, R., Petrow, P.K., Thoss, K., Gajda, M., Henzgen, S., Hecker, M., Br??uer, R. Arthritis Res. Ther. (2006) [Pubmed]
  3. Cytokine gene expression in peripheral blood mononuclear cells and tissues of cattle infected with Mycobacterium avium subsp. paratuberculosis: evidence for an inherent proinflammatory gene expression pattern. Coussens, P.M., Verman, N., Coussens, M.A., Elftman, M.D., McNulty, A.M. Infect. Immun. (2004) [Pubmed]
  4. Ex vivo induction of TNF-alpha and IL-6 mRNA in bovine whole blood by Mycobacterium paratuberculosis and mycobacterial cell wall components. Adams, J.L., Czuprynski, C.J. Microb. Pathog. (1995) [Pubmed]
  5. Simultaneous multiple immunoassays in a compact disc-shaped microfluidic device based on centrifugal force. Honda, N., Lindberg, U., Andersson, P., Hoffmann, S., Takei, H. Clin. Chem. (2005) [Pubmed]
  6. Activation of dendritic cells by liposomes prepared from phosphatidylinositol mannosides from Mycobacterium bovis bacillus Calmette-Guerin and adjuvant activity in vivo. Sprott, G.D., Dicaire, C.J., Gurnani, K., Sad, S., Krishnan, L. Infect. Immun. (2004) [Pubmed]
  7. Interleukin 17 induces cartilage collagen breakdown: novel synergistic effects in combination with proinflammatory cytokines. Koshy, P.J., Henderson, N., Logan, C., Life, P.F., Cawston, T.E., Rowan, A.D. Ann. Rheum. Dis. (2002) [Pubmed]
  8. IL-6 and its soluble receptor augment aggrecanase-mediated proteoglycan catabolism in articular cartilage. Flannery, C.R., Little, C.B., Hughes, C.E., Curtis, C.L., Caterson, B., Jones, S.A. Matrix Biol. (2000) [Pubmed]
  9. Regulation of bovine acute phase responses by recombinant interleukin-1 beta. Godson, D.L., Baca-Estrada, M.E., Van Kessel, A.G., Hughes, H.P., Morsy, M.A., Van Donkersgoed, J., Harland, R.J., Shuster, D.E., Daley, M.J., Babiuk, L.A. Can. J. Vet. Res. (1995) [Pubmed]
  10. Effects of interleukin-6 on proliferation and follicle-stimulating hormone-induced estradiol production by bovine granulosa cells in vitro: dependence on size of follicle. Alpizar, E., Spicer, L.J. Biol. Reprod. (1994) [Pubmed]
  11. Lipopolysaccharide-mediated induction of the bovine interleukin-6 gene in monocytes requires both NF-kappa B and C/EBP binding sites. Ray, A., Ray, B.K. DNA Cell Biol. (1995) [Pubmed]
  12. Molecular characterization and prokaryotic expression of buffalo (Bubalus bubalis) Interleukin-6. Premraj, A., Sreekumar, E., Nautiyal, B., Rasool, T.J. Mol. Immunol. (2006) [Pubmed]
  13. Trimellitic anhydride-conjugated serum albumin activates rat alveolar macrophages in vitro. Valstar, D.L., Schijf, M.A., Stelekati, E., Nijkamp, F.P., Bloksma, N., Henricks, P.A. Journal of occupational medicine and toxicology (London, England) (2006) [Pubmed]
  14. Interleukin 6 gene transcripts are expressed in atherosclerotic lesions of genetically hyperlipidemic rabbits. Ikeda, U., Ikeda, M., Seino, Y., Takahashi, M., Kano, S., Shimada, K. Atherosclerosis (1992) [Pubmed]
  15. Lymphocyte adhesion to brain capillary endothelial cells in vitro. de Vries, H.E., Moor, A.C., Blom-Roosemalen, M.C., de Boer, A.G., Breimer, D.D., van Berkel, T.J., Kuiper, J. J. Neuroimmunol. (1994) [Pubmed]
  16. Effects of varied EGCG and (+)-catechin concentrations on proinflammatory cytokines mrna expression in cona-stimulated primary white blood cell cultures. Sehm, J., Polster, J., Pfaffl, M.W. J. Agric. Food Chem. (2005) [Pubmed]
  17. Inhibitory effects of interleukin 6 on prostaglandin I2 production in cultured bovine vascular endothelial cells. Maruo, N., Morita, I., Ishizaki, Y., Murota, S. Arch. Biochem. Biophys. (1992) [Pubmed]
  18. Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors. Barney, M., Call, G.B., McIlmoil, C.J., Husein, O.F., Adams, A., Balls, A.G., Oliveira, G.K., Miner, E.C., Richards, T.A., Crawford, B.K., Heckmann, R.A., Bell, J.D., Judd, A.M. Endocrine (2000) [Pubmed]
  19. Cytokine mRNA profiling of peripheral blood mononuclear cells from trypanotolerant and trypanosusceptible cattle infected with Trypanosoma congolense. O'Gorman, G.M., Park, S.D., Hill, E.W., Meade, K.G., Mitchell, L.C., Agaba, M., Gibson, J.P., Hanotte, O., Naessens, J., Kemp, S.J., MacHugh, D.E. Physiol. Genomics (2006) [Pubmed]
  20. Role of interleukin 6 (IL-6)/IL-6R-induced signal tranducers and activators of transcription and mitogen-activated protein kinase/extracellular. Legendre, F., Bogdanowicz, P., Boumediene, K., Pujol, J.P. J. Rheumatol. (2005) [Pubmed]
  21. Comparison of gene transcription in cloned bovine embryos produced by different nuclear transfer techniques. Daniels, R., Hall, V.J., French, A.J., Korfiatis, N.A., Trounson, A.O. Mol. Reprod. Dev. (2001) [Pubmed]
  22. Shear stress increases the release of interleukin-1 and interleukin-6 by aortic endothelial cells. Sterpetti, A.V., Cucina, A., Morena, A.R., Di Donna, S., D'Angelo, L.S., Cavalarro, A., Stipa, S. Surgery (1993) [Pubmed]
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