Bacterial infection of the mammalian bloodstream can lead to overwhelming sepsis, a potentially fatal syndrome of irreversible cardiovascular collapse (shock) and critical organ failure. Cachectin, also known as tumour necrosis factor, is a macrophage-derived peptide hormone released in response to bacterial lipopolysaccharide, and it has been implicated as a principal mediator of endotoxic shock, although its function in bacterial sepsis is not known. Anaesthetized baboons were passively immunized against endogenous cachectin and subsequently infused with an LD100 dose of live Escherichia coli. Control animals (not immunized against cachectin) developed hypotension followed by lethal renal and pulmonary failure. Neutralizing monoclonal anti-cachectin antibody fragments (F(ab′)2) administered to baboons only one hour before bacterial challenge protected against shock, but did not prevent critical organ failure. Complete protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion. These results indicate that cachectin is a mediator of fatal bacteraemic shock, and suggest that antibodies against cachectin offer a potential therapy of life-threatening infection.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
1. Kreger, B. E. W., Craven, D. E. & McCabe, W. R. Am. J. Med. 68, 344-355 (1980). 2. Ziegler, E. J. el al New Engl. J. Med, 307, 1225-1230 (1982). 3. Gilbert, R. P. Physiol. Rev. 40, 245-279 (1960). 4. Beutler, B. & Cerami, A. Nature 320, 584-588 (1986). 5. Beutler, B. & Cerami, A. New Engl. J. Med. 316, 379-385 (1987). 6. Tracey, K. J., Lowry, S. F. & Cerami, A. in TNF and Related Cytotoxins. CIBA Found. Symp. 131, 88-108 (Wiley, London, 1987). 7. Tracey, K. J., Lowry, S. F. & Cerami, A. J. infect. Dis. (in the press). 8. Beutler, B., Milsark, I. W. & Cerami, A. J. Immun. 135, 3972-3977 (1985). 9. Tracey, K. J. et al. Science 234, 470-474 (1986). 10. Tracey, K. J. et al. Surg. gynecol. Obstet. 164, 415-422 (1987). 11. Beutler, B., Milsark, I. W. & Cerami, A. Science 229, 869-871 (1985). 12. Cryer, P. E., Herman, C. M. & Sode, J. Ann. Surg. 174, 91-100 (1971). 13. Coalson, J. J., Hinshaw, L. B., Guenter, C. A., Berrel, E. L. & Greenfield, L. J. Lab. Invest. 32, 561-569 (1975). 14. Hesse, D. G. et al. Surg. gynecol. Obstet. (in the press). 15. Lowry, S. F. in Advances in Host Defense Mechanisms Vol. 6 (eds Gallin, J. I. & Fauci, A. S.) 169-190 (Raven, New York, 1986). 16. McCabe, W. R. New Engl. J. Med. 288, 21-23 (1973). 17. Dinarello, C. A. et al. J. exp. Med. 163, 1433-1450 (1986). 18. Darius, H., Lefer, D. J., Smith, J. B. & Lefer, A. M. Science 232, 58-60 (1986). 19. Chang, S. W., Feddersen, C. O., Henson, P. M. & Voelkel, N. F. J. din. Invest. 79,1498-1509 (1987). 20. Scuderi, P. et al. Lancet ii, 1364-1365 (1986). 21. Tracey, K. J. et al. Surg. Forum 37, 13-15 (1986). 22. Waage, A., Halstensen, A. & Espevik, T. Lancet i, 355-357 (1987). 23. Pool, J. L. Surg. gynecol. Obstet. 132, 1-9 (1971). 24. Parham, P. J. Immun. 131, 2895-2899 (1983). 25. Peters, P. M. et al. J. Immun. 137, 2592-2598 (1986). 26. Carswell, E. A. et al. Proc. natn. Acad. Sci. U.S.A. 72, 3666-3670 (1975). 27. Passon, P. G. & Peuler, J. D. Analyt. Biochem. 51, 618-631 (1973). 28. Aquilar-Parada, A., Eisentraut, E. M. & Unger, R. H. Diabetes 18, 717-723 (1969).
About this article
Brain, Behavior, and Immunity (2019)
Hemodynamic consequences of intravenously given E. coli suspension: observations in a fulminant sepsis model in pigs, a descriptive case–control study
European Journal of Medical Research (2019)
Role of Pseudomonas aeruginosa lipopolysaccharides in modulation of biofilm and virulence factors of Enterobacteriaceae
Annals of Microbiology (2019)
Journal of Cellular Biochemistry (2019)
International Journal of Biological Macromolecules (2019)