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Gene Review

TNF  -  tumor necrosis factor

Ovis aries

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Disease relevance of TNF-alpha


Psychiatry related information on TNF-alpha


High impact information on TNF-alpha


Chemical compound and disease context of TNF-alpha


Biological context of TNF-alpha


Anatomical context of TNF-alpha

  • A slight increase in serum albumin, paralleling the changes in leukocyte numbers, was observed after infusion of IL-1 beta and, to some extent, TNF-alpha [13].
  • The cell accumulation induced by IL-1 beta or TNF-alpha was dose and time dependent in lactating udders, and time-dependent in teat cisterns [13].
  • Although the three cytokines mentioned have little or no effect on viability of cultured luteal cells when administered separately, combined treatment with TNF-alpha and IFN-gamma results in a substantial decrease in the number of viable cells [14].
  • The inflammatory cytokines tumour necrosis factor-alpha (TNF alpha), interleukin 1 (IL-1) and interleukin 6 (IL-6) have been demonstrated to influence pituitary hormone synthesis directly and via the hypothalamus [15].
  • It seems that TNF-alpha plays a role in early activation of splenic macrophages which is important in controlling the outcome of an infection [16].

Associations of TNF-alpha with chemical compounds

  • A more robust response to BK (3.2+/-0.25 x 10(6) cells cavity(-1)) was seen in animals pretreated with captopril, but this was still smaller than the responses to IL-1beta or TNF-alpha (15 pmol: 23+/-2.2 x 10(6) and 75 pmol: 29.5+/-2 x 10(6) cells cavity(-1), respectively) [17].
  • Tezosentan completely prevented the changes in PKC-alpha in both the cytosolic and the membrane fractions, concomitantly causing a further increase in the plasma concentrations of ET-1, TNF-alpha, and IL-8 [18].
  • Levels of common glycoprotein alpha-subunit and follicle stimulating hormone-beta (FSH beta) subunit mRNA were unaffected by TNF alpha [15].
  • In contrast, medium alone, polystyrene beads, and productive infection by OvLV did not induce TNF-alpha activity in PAM cultures [19].
  • A suprapharmacological concentration of indomethacin also was necessary to protect ovarian surface epithelial cells from a (prostaglandin-independent) cytotoxic effect of TNF-alpha in vitro [20].

Regulatory relationships of TNF-alpha

  • We conclude that TNF alpha can regulate both GH and IL-6 synthesis in dispersed ovine pituitary cells [15].

Other interactions of TNF-alpha

  • Plasma TNF-alpha concentrations increased transiently within 1 h of interleukin-1 beta injection, indicating that an acute-phase response had been initiated [1].
  • Infected intestinal tissues had significantly increased mRNA for TNF-alpha, IL-1beta and IL-6 but TGF-beta1 and GM-CSF mRNA levels were significantly different from controls [2].
  • IgE, TNF alpha, IL1 beta, IL4 and IFN gamma gene polymorphisms in sheep selected for resistance to fleece rot and flystrike [21].
  • These relationships notwithstanding, expression of the IL-10 and TNF-alpha genes declined significantly in afferent lymph cells but not in efferent lymph cells during infection [22].
  • Arteries incubated for 6 h with interferon-gamma (IFN-gamma, 10 ng ml(-1)) and tumour necrosis factor-alpha (TNF-alpha, 5 ng ml(-1)) exhibited greater relaxation to BK (E(max)-50.0+/-5.1%) than polymyxin B-treated controls (E(max)-33.1+/-4.0%), but did not differ in their response to PE [23].

Analytical, diagnostic and therapeutic context of TNF-alpha


  1. Follistatin concentrations in male sheep increase following sham castration/castration or injection of interleukin-1 beta. Phillips, D.J., Hedger, M.P., McFarlane, J.R., Klein, R., Clarke, I.J., Tilbrook, A.J., Nash, A.D., de Kretser, D.M. J. Endocrinol. (1996) [Pubmed]
  2. Increased intestinal TNF-alpha, IL-1 beta and IL-6 expression in ovine paratuberculosis. Alzuherri, H.M., Woodall, C.J., Clarke, C.J. Vet. Immunol. Immunopathol. (1996) [Pubmed]
  3. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Wright, S.D., Ramos, R.A., Tobias, P.S., Ulevitch, R.J., Mathison, J.C. Science (1990) [Pubmed]
  4. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. Moreira, A.L., Sampaio, E.P., Zmuidzinas, A., Frindt, P., Smith, K.A., Kaplan, G. J. Exp. Med. (1993) [Pubmed]
  5. Endotoxin infusion in anesthetized sheep is associated with intrapulmonary sequestration of leukocytes that immunohistochemically express tumor necrosis factor-alpha. Cirelli, R.A., Carey, L.A., Fisher, J.K., Rosolia, D.L., Elsasser, T.H., Caperna, T.J., Gee, M.H., Albertine, K.H. J. Leukoc. Biol. (1995) [Pubmed]
  6. Intracerebroventricular injection of TNF-alpha promotes sleep and is recovered in cervical lymph. Dickstein, J.B., Moldofsky, H., Lue, F.A., Hay, J.B. Am. J. Physiol. (1999) [Pubmed]
  7. Stimulation of tumor necrosis factor-alpha production by mycoplasmas and inhibition by dexamethasone in cultured astrocytes. Brenner, T., Yamin, A., Abramsky, O., Gallily, R. Brain Res. (1993) [Pubmed]
  8. Migratory responses of ovine neutrophils to inflammatory mediators in vitro and in vivo. Mulder, K., Colditz, I.G. J. Leukoc. Biol. (1993) [Pubmed]
  9. Effect of Salmonella endotoxin administered to the pregnant sheep at 133-142 days gestation on fetal oxygenation, maternal and fetal adrenocorticotropic hormone and cortisol, and maternal plasma tumor necrosis factor alpha concentrations. Schlafer, D.H., Yuh, B., Foley, G.L., Elssaser, T.H., Sadowsky, D., Nathanielsz, P.W. Biol. Reprod. (1994) [Pubmed]
  10. Sequence of the cDNA encoding ovine tumor necrosis factor-alpha: problems with cloning by inverse PCR. Green, I.R., Sargan, D.R. Gene (1991) [Pubmed]
  11. Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection. Konnai, S., Usui, T., Ikeda, M., Kohara, J., Hirata, T., Okada, K., Ohashi, K., Onuma, M. Virology (2005) [Pubmed]
  12. Tumor necrosis factor alpha regulates collagenolytic activity in preovulatory ovine follicles: relationship to cytokine secretion by the oocyte-cumulus cell complex. Johnson, M.L., Murdoch, J., Van Kirk, E.A., Kaltenbach, J.E., Murdoch, W.J. Biol. Reprod. (1999) [Pubmed]
  13. Cytokine-induced inflammation in the ovine teat and udder. Persson, K., Colditz, I.G., Flapper, P., Franklin, N.A., Seow, H.F. Vet. Immunol. Immunopathol. (1996) [Pubmed]
  14. Involvement of immune cells in regulation of ovarian function. Pate, J.L. J. Reprod. Fertil. Suppl. (1995) [Pubmed]
  15. Effects of tumour necrosis factor-alpha on growth hormone and interleukin 6 mRNA in ovine pituitary cells. Nash, A.D., Brandon, M.R., Bello, P.A. Mol. Cell. Endocrinol. (1992) [Pubmed]
  16. Early activation of splenic macrophages by tumor necrosis factor alpha is important in determining the outcome of experimental histoplasmosis in mice. Wu-Hsieh, B.A., Lee, G.S., Franco, M., Hofman, F.M. Infect. Immun. (1992) [Pubmed]
  17. Effect of a kinin B2 receptor antagonist on LPS- and cytokine-induced neutrophil migration in rats. Santos, D.R., Calixto, J.B., Souza, G.E. Br. J. Pharmacol. (2003) [Pubmed]
  18. Tezosentan-induced attenuation of lung injury in endotoxemic sheep is associated with reduced activation of protein kinase C. Kuklin, V., Kirov, M., Sovershaev, M., Andreasen, T., Ingebretsen, O.C., Ytrehus, K., Bjertnaes, L. Critical care (London, England) (2005) [Pubmed]
  19. Differential induction of tumor necrosis factor alpha in ovine pulmonary alveolar macrophages following infection with Corynebacterium pseudotuberculosis, Pasteurella haemolytica, or lentiviruses. Ellis, J.A., Lairmore, M.D., O'Toole, D.T., Campos, M. Infect. Immun. (1991) [Pubmed]
  20. Prostaglandin-independent anovulatory mechanism of indomethacin action: inhibition of tumor necrosis factor alpha-induced sheep ovarian cell apoptosis. Murdoch, W.J., Lund, S.A. Biol. Reprod. (1999) [Pubmed]
  21. IgE, TNF alpha, IL1 beta, IL4 and IFN gamma gene polymorphisms in sheep selected for resistance to fleece rot and flystrike. Engwerda, C.R., Dale, C.J., Sandeman, R.M. Int. J. Parasitol. (1996) [Pubmed]
  22. Increased expression of interleukin-5 (IL-5), IL-13, and tumor necrosis factor alpha genes in intestinal lymph cells of sheep selected for enhanced resistance to nematodes during infection with Trichostrongylus colubriformis. Pernthaner, A., Cole, S.A., Morrison, L., Hein, W.R. Infect. Immun. (2005) [Pubmed]
  23. The role of nitric oxide in the responses of the ovine digital artery to vasoactive agents and modification of these responses by endotoxin and cytokines. Pawson, P., Reid, J., Nolan, A.M. Br. J. Pharmacol. (2000) [Pubmed]
  24. Coronary microembolization: the role of TNF-alpha in contractile dysfunction. Dörge, H., Schulz, R., Belosjorow, S., Post, H., van de Sand, A., Konietzka, I., Frede, S., Hartung, T., Vinten-Johansen, J., Youker, K.A., Entman, M.L., Erbel, R., Heusch, G. J. Mol. Cell. Cardiol. (2002) [Pubmed]
  25. Minimal lung and systemic responses to TNF-alpha in preterm sheep. Ikegami, M., Moss, T.J., Kallapur, S.G., Mulrooney, N., Kramer, B.W., Nitsos, I., Bachurski, C.J., Newnham, J.P., Jobe, A.H. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
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