Lipopolysaccharide, but Not Lethal Infection, Releases Tumor Necrosis Factor in Mice
An endogenously produced cytokine, tumor necrosis factor (TNF), is thought to be an important mediator in the pathophysiology of gram-negative sepsis (10). Infusions of TNF in animals reproduce the metabolic, hormonal, hemodynamic, and histopathologic finding seen in lethal gram-negative infection (7, 11). Pretreatment with polyclonal anti-TNF antibodies was shown to reduce endotoxin (LPS) lethality in mice (1). Passive immunization with monoclonal antibodies against recombinant human TNF conferred complete protection against shock and death in baboons challenged with an otherwise lethal infusion of E. coli (9). Measurable circulating levels of TNF have been found in animals following a lethal bolus infusion of LPS (2, 8) or live gram-negative bacteria (6, 9), while little has been reported concerning TNF produttion in other models of lethal gram-negative infection.
KeywordsTumor Necrosis Factor Passive Immunization Serum Tumor Necrosis Factor Recombinant Human Tumor Necrosis Factor Tumor Necrosis Factor Activity
Unable to display preview. Download preview PDF.
- 1.Beutler, B. A., Milsack, I. W. and Cerami, A., 1985, Passive immunization against cachectin tumor necrosis factor protects mice from lethal effects of endotoxin. Science 229: 869–871.Google Scholar
- 2.Beutler, B. A., Milsack, I. W. and Cerami, A., 1985, Cachectin/tumor necrosis factor: production, distribution and metabolic fate in vivo. J. Immunol. 135: 3972–3977.Google Scholar
- 3.Bradley, S. G., 1985, Interactions between endotoxin and protein synthesis, in: “Handbook of Endotoxin,” Vol. 3, Cellular Biology of Endotoxin, L. J. Berry, ed., Elsevier, Amsterdam, New York, p. 340–371.Google Scholar
- 4.Flick, D. A. and Gifford, G. E., 1983, Comparison of in vitro cytotoxic assays for tumor necrosis factor. J. Immunol. Methods 68: 167–175.Google Scholar
- 5.Golenbock, D. T., Leggett, J. E., Rasmussen, P., Craig, W. A., Raetz, C. R. H. and Proctor, R. A., 1988, Lipid X protects mice against fatal gram-negative infection. Infect. Immun. 56: 779–784.Google Scholar
- 6.Hesse, D. G., Tracey, K. J., Fong, Y., et al., 1988, Cytokine appearance in human endotoxemia and primate bacteremia. Surg. Gynecol. Obstet. 166: 147–153.Google Scholar
- 7.Mannel, D. N., Northoff, H., Bauss, F. and Felk, W., 1987, Tumor necrosis factor: cytokine involved in toxic effects of endotoxin. Rev. Infect. Dis. 9: S602–S606.Google Scholar
- 8.Rothstein, J. L. and Schreiber, H., 1987, Relationship of tumor necrosis factor and endotoxin to macrophage cytotoxicity, hemorrhagic necrosis and lethal shock, in: “Tumor necrosis factor and related cytotoxins,” J. Wiley, ed., London, England (Ciba Found. Symp. 131 ), p. 124–135.Google Scholar
- 9.Tracey, K. J., Fong, Y., Hesse, A. G., et al., 1987, Anti-cachectin/ TNF monoclonal antibodies prevent septic shock during lethal bacteremia. Nature 330: 662–664.Google Scholar
- 10.Tracey, K. J., Lowry, S. F. and Cerami, A., 1988, Cachectin: a hormone that triggers acute shock and chronic cachexia. J. Infect. Dis. 157: 413–420.Google Scholar
- 11.Tracey, K. J., Lowry, S. F., Fahey, T. J., et al., 1987, Cachectin/ tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg. Gynecol. Obstet. 164: 415–422.Google Scholar