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Gene Review

IL6  -  interleukin 6 (interferon, beta 2)

Canis lupus familiaris

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Disease relevance of IL6


High impact information on IL6

  • However, investigation of interleukin 6 (IL-6) revealed that recombinant IL-6 stimulated myocyte adhesiveness for ZAS-stimulated neutrophils (ED50 = 0.002 U/ml) and expression of ICAM-1 by isolated myocytes [5].
  • These results indicate that cytokines capable of promoting neutrophil-myocyte adhesion occur in extracellular fluid during reperfusion of ischemic myocardium, and that one of these cytokines is IL-6 [5].
  • Myocytes stimulated with preischemic lymph showed minimal or no IL-6 mRNA expression, whereas myocytes stimulated with tumor necrosis factor-alpha, IL-1beta, lipopolysaccharide, or postischemic lymph showed a strong IL-6 mRNA induction [3].
  • Unstimulated myocytes showed no significant IL-6 mRNA expression [3].
  • We have previously demonstrated the induction of IL-6 in the ischemic myocardium, and the current study addresses the cells of origin of IL-6 [3].

Chemical compound and disease context of IL6

  • To test the hypothesis that cytokines play a role in ischemic or reperfusion injury, we measured tumor necrosis factor (TNF) and interleukin-6 (IL-6) in pentobarbital-anesthetized dogs before, during, and after coronary occlusion lasting 60 min [6].
  • Because the origin of endotoxemia may affect the reactions to endotoxin, we compared the induction of tumor necrosis factor (TNF), interleukin-6 (IL-6), hormones, and glucose production after endotoxin (1.0 microg/kg Escherichia coli 0111:B4) administration into a peripheral (n = 8) versus the portal (n = 8) vein in anesthetized dogs [7].
  • These data support the hypothesis that sepsis initiates a cascade of mediators with the cytokines TNF and IL-6 being proximal events which in turn stimulate the next level, with ibuprofen probably exerting its inhibitory effect distal to this point in the cascade [8].
  • The brain-dead group treated with LPS (n = 6) responded with a significant elevation in IL-6-like and TNF-like activities compared with the vehicle-treated group [9].

Biological context of IL6


Anatomical context of IL6


Associations of IL6 with chemical compounds

  • The plasma was analysed with respect to roxithromycin, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) [15].
  • As measured by P-selectin expression, enhanced responsiveness to the strong agonist platelet activating factor (PAF) was also observed in the IL-6-treated dogs [10].
  • The EC50 of thiazole orange-positive platelets from IL-6-treated dogs decreased dramatically by day 5 to 46.5% +/- 13.1% (n = 4) of control values (P < 0.001), whereas TPO-treated dogs did not significantly change [16].
  • Blood for analysis of tumor necrosis factor (TNF) and IL-6 was sampled from the femoral artery and the portal, hepatic, and splenic (only in controls) veins [4].
  • CONCLUSIONS: DHEA decreased the IL-6 concentration in the supernatant of LPS-stimulated DH82 cells by inhibiting the sequestration of IkappaBalpha, which is necessary for the activation of nuclear factor-kappa B [17].

Other interactions of IL6

  • The objective of this study was to quantify the expression of mRNA encoding Th(1)-like [interferon (IFN)-gamma, interleukin (IL)-2 and IL-12], Th(2)-like [IL-4 and IL-6] and immunomodulatory cytokines [IL-10 and transforming growth factor (TGF)-beta] in lesional ImR-LPP, nonlesional ImR-LPP and healthy control pedal skin [18].

Analytical, diagnostic and therapeutic context of IL6

  • This new mechanism, in which TIL manufacture high concentrations of IL-6 to block tumor TGF-beta1 anti-LAK activity, has potential applications in cancer immunotherapy and tumor prognosis [1].
  • This study analyzed temporal expression levels of IL-1beta, IL-2, IL-6, IL-8, IFN-gamma, and TNF-alpha mRNA by peripheral blood leukocytes from dogs experimentally infected with a new virulent strain of E. canis by using real-time RT-PCR [13].
  • Northern blot with ICAM-1 probe revealed ICAM-1 expression under every condition that demonstrated IL-6 induction [3].
  • Supernatant IL-6 levels were measured by enzyme-linked immunosorbent assay, and cellular cytoplasmic IkappaBalpha protein expression measured by Western blot analysis [17].


  1. Tumor-infiltrating lymphocyte secretion of IL-6 antagonizes tumor-derived TGF-beta 1 and restores the lymphokine-activated killing activity. Hsiao, Y.W., Liao, K.W., Hung, S.W., Chu, R.M. J. Immunol. (2004) [Pubmed]
  2. IL-6 and TNF-alpha production during active canine visceral leishmaniasis. de Lima, V.M., Peiro, J.R., de Oliveira Vasconcelos, R. Vet. Immunol. Immunopathol. (2007) [Pubmed]
  3. Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Gwechenberger, M., Mendoza, L.H., Youker, K.A., Frangogiannis, N.G., Smith, C.W., Michael, L.H., Entman, M.L. Circulation (1999) [Pubmed]
  4. The decrease in nonsplenic interleukin-6 (IL-6) production after splenectomy indicates the existence of a positive feedback loop of IL-6 production during endotoxemia in dogs. Moeniralam, H.S., Bemelman, W.A., Endert, E., Koopmans, R., Sauerwein, H.P., Romijn, J.A. Infect. Immun. (1997) [Pubmed]
  5. Neutrophil adherence to isolated adult cardiac myocytes. Induction by cardiac lymph collected during ischemia and reperfusion. Youker, K., Smith, C.W., Anderson, D.C., Miller, D., Michael, L.H., Rossen, R.D., Entman, M.L. J. Clin. Invest. (1992) [Pubmed]
  6. Tumor necrosis factor and interleukin-6 are not elevated in venous blood from ischemic canine myocardium. Field, G., Conn, C.A., McClanahan, T.B., Nao, B.S., Kluger, M.J., Gallagher, K.P. Proc. Soc. Exp. Biol. Med. (1994) [Pubmed]
  7. Origin of endotoxemia influences the metabolic response to endotoxin in dogs. Moeniralam, H.S., Bemelman, W.A., Romijn, J.A., Endert, E., Ackermans, M.T., van Lanschot, J.J., Hermsen, R.C., Sauerwein, H.P. J. Surg. Res. (1997) [Pubmed]
  8. Ibuprofen intervention in canine septic shock: reduction of pathophysiology without decreased cytokines. Coran, A.G., Drongowski, R.A., Paik, J.J., Remick, D.G. J. Surg. Res. (1992) [Pubmed]
  9. Plasma profiles of IL-6-like and TNF-like activities in brain-dead dogs. Huber, T.S., Kluger, M.J., Harris, S.P., D'Alecy, L.G. Am. J. Physiol. (1991) [Pubmed]
  10. Alteration of platelet function in dogs mediated by interleukin-6. Peng, J., Friese, P., George, J.N., Dale, G.L., Burstein, S.A. Blood (1994) [Pubmed]
  11. The effect of interleukin-6 on bacterial translocation in acute canine pancreatitis. Liu, Q., Djuricin, G., Nathan, C., Gattuso, P., Weinstein, R.A., Prinz, R.A. Int. J. Pancreatol. (2000) [Pubmed]
  12. Proinflammatory cytokine activities, matrix metalloproteinase-3 activity, and sulfated glycosaminoglycan content in synovial fluid of dogs with naturally acquired cranial cruciate ligament rupture. Fujita, Y., Hara, Y., Nezu, Y., Schulz, K.S., Tagawa, M. Veterinary surgery : VS : the official journal of the American College of Veterinary Surgeons. (2006) [Pubmed]
  13. Cytokine Gene Expression by Peripheral Blood Leukocytes in Dogs Experimentally Infected with a New Virulent Strain of Ehrlichia canis. Unver, A., Huang, H., Rikihisa, Y. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  14. Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Frangogiannis, N.G., Lindsey, M.L., Michael, L.H., Youker, K.A., Bressler, R.B., Mendoza, L.H., Spengler, R.N., Smith, C.W., Entman, M.L. Circulation (1998) [Pubmed]
  15. Pharmacokinetic/Pharmacodynamic modelling of roxithromycin for the inhibitory effect of tumour necrosis factor-alpha and interleukin-6 production in dogs. Lim, J.H., Park, B.K., Yun, H.I. Journal of veterinary medicine. A, Physiology, pathology, clinical medicine. (2006) [Pubmed]
  16. Relative reactivity of platelets from thrombopoietin- and interleukin-6-treated dogs. Peng, J., Friese, P., Wolf, R.F., Harrison, P., Downs, T., Lok, S., Dale, G.L., Burstein, S.A. Blood (1996) [Pubmed]
  17. Effect of dehydroepiandrosterone on lipopolysaccharide-induced interleukin-6 production in DH82 cultured canine macrophage cells. Kim, S.K., Shin, M.S., Jung, B.K., Shim, J.Y., Won, H.S., Lee, P.R., Kim, A. J. Reprod. Immunol. (2006) [Pubmed]
  18. Evaluation of Th(1)-like, Th(2)-like and immunomodulatory cytokine mRNA expression in the skin of dogs with immunomodulatory-responsive lymphocytic-plasmacytic pododermatitis. Breathnach, R.M., Fanning, S., Mulcahy, G., Bassett, H.F., Jones, B.R., Daly, P. Vet. Dermatol. (2006) [Pubmed]
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