Disease relevance of TNF-alpha

• Tumour necrosis factor-alpha (TNF-alpha), a sensitive maker of an acute-phase response, was undetectable in plasma, indicating that the FS response was not induced by trauma due to surgery [1].
• Increased intestinal TNF-alpha, IL-1 beta and IL-6 expression in ovine paratuberculosis [2].
• Excess secretion of TNF-alpha causes endotoxic shock, an often fatal complication of infection [3].
• The selective inhibition of TNF-alpha production makes thalidomide an ideal candidate for the treatment of inflammatory conditions where TNF-alpha-induced toxicities are observed and where immunity must remain intact [4].
• We conclude that TNF-alpha-producing leukocytes accumulate in the pulmonary circulation during endotoxemia [5].

Psychiatry related information on TNF-alpha

• Polysomnographic recordings of four animals showed that TNF-alpha induced a significant increase in slow-wave sleep at postinjection hours 4 and 5 [6].
• Elevated levels of tumor necrosis factor-alpha (TNF alpha) and other cytokines and eicosanoids in the central nervous system (CNS) have been noted in several human neurologic diseases, including multiple sclerosis and AIDS dementia [7].

High impact information on TNF-alpha

• CD14, a differentiation antigen of monocytes, was found to bind complexes of LPS and LBP, and blockade of CD14 with monoclonal antibodies prevented synthesis of TNF-alpha by whole blood incubated with LPS [3].
• Leukocytes respond to lipopolysaccharide (LPS) at nanogram per milliliter concentrations with secretion of cytokines such as tumor necrosis factor-alpha (TNF-alpha) [3].
• We have examined the mechanism of thalidomide inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production and found that the drug enhances the degradation of TNF-alpha mRNA [4].
• Inhibition of TNF-alpha production was selective, as other LPS-induced monocyte cytokines were unaffected [4].
• Pentoxifylline and dexamethasone, two other inhibitors of TNF-alpha production, are known to exert their effects by means of different mechanisms, suggesting that the three agents inhibit TNF-alpha synthesis at distinct points of the cytokine biosynthetic pathway [4].

Chemical compound and disease context of TNF-alpha

• Of these mediators LTB4, ZAP, IL-1 alpha, TNF-alpha, IFN-gamma, and IL-8 have been reported to induce neutrophil accumulation in skin of sheep, and in the current study E. coli endotoxin was a potent inducer of 111In-labeled neutrophil accumulation and plasma leakage in skin [8].
• In contrast, leukotriene B4 (LTB4), platelet-activating factor (PAF), interleukin-1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), N-formyl-methionine-leucyl-phenylalanine (fMLP), and endotoxins from Escherichia coli and Pseudomonas aeruginosa failed to induce neutrophil migration in vitro [8].
• 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 [9].

Biological context of TNF-alpha

• We have cloned and sequenced the ovine tumor necrosis factor-alpha (TNF-alpha)-encoding cDNA, using gene amplification by polymerase chain reaction (PCR) technology, to aid studies of assorted diseases in this species [10].
• We hypothesized that a source of this TNF-alpha is the pool of leukocytes that accumulate in the pulmonary circulation [5].
• Most cells expressing TNF-RII in PL cattle were CD5+ or sIgM+ cells and these cells showed resistance to TNF-alpha-induced apoptosis [11].
• To our knowledge, this is the first report specifying that up-regulation of collagenase expression is a target mode of TNF-alpha action in preovulatory follicles [12].
• Intrafollicular injection of TNF-alpha antibodies at 12 h after GnRH negated the rise in follicular collagenolytic bioactivity (and is known to block ovulation in the sheep) [12].

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

• Supernatants from in vitro intestinal cultures were assayed for TNF-alpha activity using the PK(15)-1512 cytotoxicity bioassay and levels were significantly raised in diseased samples [2].
• Sequence of the cDNA encoding ovine tumor necrosis factor-alpha: problems with cloning by inverse PCR [10].
• In situ hybridization for TNF-alpha mRNA identified viable cardiomyocytes surrounding the microinfarcts as the major source of TNF-alpha [24].
• TNF-alpha given into the airways at birth increased granulocytes in the bronchoalveolar lavage fluid of ventilated preterm lungs and decreased the mRNA for surfactant protein C but did not adversely effect postnatal lung function [25].
• There was an increase in TNF-alpha (immunoassay) in antral fluid of preovulatory follicles at 18 h after GnRH, which was related to tissue collagenolytic bioactivity (radiolabeled type I substrate digestion by enzymatic extract) and collagen (hydroxyproline) depletion [12].

References