Modulation of tumor necrosis factor activities by a potential anticachexia compound, hydrazine sulfate.
Experiments were performed to determine the effects of hydrazine sulfate (HS), a potential anti-cachexia agent, on tumor necrosis factor activities (cachectin/TNF) in vitro. We present evidence that HS significantly inhibits the lytic activity of TNF on L-929 cells, that HS has no direct effect on TNF itself, and that the minimum amount of time for maximum inhibition of TNF activity to occur after HS treatment is between 1 and 4 h. In addition to HS's effect on the cytolytic activity, we also determined its effect on the antiviral activity of TNF. We found that HS greatly potentiates TNF antiviral activity, while having no significant antiviral activity itself over a range of concentrations, that the potentiation was likely between HS and TNF-induced interferon-B1, and was maximal following 4 and 8 h of treatment with HS. Although the lytic activity of TNF has not been directly correlated with its cachectic activities, these studies provide evidence for an effect of HS on cachectin and its role in the wasting process. Furthermore, a rationale is provided for use of HS in conjunction with TNF for prevention and/or treatment of viral infection.
Hughes
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Department of Microbiology, University of Texas Medical Branch, Galveston, TX 77550.
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D000818:Animals; D000998:Antiviral Agents; D002100:Cachexia / Q000188:drug therapy*; D002478:Cells, Cultured; D003603:Cytotoxins / Q000276:immunology; D004357:Drug Synergism; D006834:Hydrazines / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000998:Antiviral Agents; D003603:Cytotoxins; D006834:Hydrazines; D014409:Tumor Necrosis Factor-alpha; C029424:hydrazine