Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Jun;84(3):411–414.

Prevention of human TNF-induced cutaneous Shwartzmann reaction and acute mortality in mice treated with anti-human TNF monoclonal antibodies.

G E Grau 1, C Vesin 1, D De Groote 1, D Delacroix 1, C Gysler 1, P F Piguet 1, P H Lambert 1
PMCID: PMC1535417  PMID: 2044219

Abstract

We studied monoclonal antibodies (MoAbs) directed against human tumour necrosis factor (TNF) for their capacity to prevent toxic or lethal effects of TNF. Two experimental models involving recombinant human TNF (rhTNF) in mice were used: the Shwartzmann reaction, and the lethality after D-galactosamine sensitization. Two MoAbs were found to be protective in both models. These MoAbs prevented mortality when given 6 h, 4 h, or 15 min before rhTNF injection but were not effective if given after TNF. In addition, our results point out that in vitro binding and even neutralizing capacities of anti-hTNF MoAbs do not necessarily reflect their protective efficacy in vivo. Therefore, the models studied here might be useful to evaluate anti-h TNF MoAbs before clinical use.

Full text

PDF
411

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  2. Calandra T., Baumgartner J. D., Grau G. E., Wu M. M., Lambert P. H., Schellekens J., Verhoef J., Glauser M. P. Prognostic values of tumor necrosis factor/cachectin, interleukin-1, interferon-alpha, and interferon-gamma in the serum of patients with septic shock. Swiss-Dutch J5 Immunoglobulin Study Group. J Infect Dis. 1990 May;161(5):982–987. doi: 10.1093/infdis/161.5.982. [DOI] [PubMed] [Google Scholar]
  3. Girardin E., Grau G. E., Dayer J. M., Roux-Lombard P., Lambert P. H. Tumor necrosis factor and interleukin-1 in the serum of children with severe infectious purpura. N Engl J Med. 1988 Aug 18;319(7):397–400. doi: 10.1056/NEJM198808183190703. [DOI] [PubMed] [Google Scholar]
  4. Grau G. E., Fajardo L. F., Piguet P. F., Allet B., Lambert P. H., Vassalli P. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science. 1987 Sep 4;237(4819):1210–1212. doi: 10.1126/science.3306918. [DOI] [PubMed] [Google Scholar]
  5. Grau G. E., Taylor T. E., Molyneux M. E., Wirima J. J., Vassalli P., Hommel M., Lambert P. H. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med. 1989 Jun 15;320(24):1586–1591. doi: 10.1056/NEJM198906153202404. [DOI] [PubMed] [Google Scholar]
  6. Lehmann V., Freudenberg M. A., Galanos C. Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med. 1987 Mar 1;165(3):657–663. doi: 10.1084/jem.165.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Michie H. R., Manogue K. R., Spriggs D. R., Revhaug A., O'Dwyer S., Dinarello C. A., Cerami A., Wolff S. M., Wilmore D. W. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med. 1988 Jun 9;318(23):1481–1486. doi: 10.1056/NEJM198806093182301. [DOI] [PubMed] [Google Scholar]
  8. Michie H. R., Spriggs D. R., Manogue K. R., Sherman M. L., Revhaug A., O'Dwyer S. T., Arthur K., Dinarello C. A., Cerami A., Wolff S. M. Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings. Surgery. 1988 Aug;104(2):280–286. [PubMed] [Google Scholar]
  9. Piguet P. F., Grau G. E., Allet B., Vassalli P. Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs.-host disease. J Exp Med. 1987 Nov 1;166(5):1280–1289. doi: 10.1084/jem.166.5.1280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Piguet P. F., Grau G. E., Vassalli P. Subcutaneous perfusion of tumor necrosis factor induces local proliferation of fibroblasts, capillaries, and epidermal cells, or massive tissue necrosis. Am J Pathol. 1990 Jan;136(1):103–110. [PMC free article] [PubMed] [Google Scholar]
  11. Rothstein J. L., Schreiber H. Synergy between tumor necrosis factor and bacterial products causes hemorrhagic necrosis and lethal shock in normal mice. Proc Natl Acad Sci U S A. 1988 Jan;85(2):607–611. doi: 10.1073/pnas.85.2.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Talmadge J. E., Bowersox O., Tribble H., Lee S. H., Shepard H. M., Liggitt D. Toxicity of tumor necrosis factor is synergistic with gamma-interferon and can be reduced with cyclooxygenase inhibitors. Am J Pathol. 1987 Sep;128(3):410–425. [PMC free article] [PubMed] [Google Scholar]
  13. Tracey K. J., Beutler B., Lowry S. F., Merryweather J., Wolpe S., Milsark I. W., Hariri R. J., Fahey T. J., 3rd, Zentella A., Albert J. D. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470–474. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  14. Tracey K. J., Fong Y., Hesse D. G., Manogue K. R., Lee A. T., Kuo G. C., Lowry S. F., Cerami A. Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature. 1987 Dec 17;330(6149):662–664. doi: 10.1038/330662a0. [DOI] [PubMed] [Google Scholar]
  15. Tracey K. J., Vlassara H., Cerami A. Cachectin/tumour necrosis factor. Lancet. 1989 May 20;1(8647):1122–1126. doi: 10.1016/s0140-6736(89)92394-5. [DOI] [PubMed] [Google Scholar]
  16. Waage A., Halstensen A., Espevik T. Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease. Lancet. 1987 Feb 14;1(8529):355–357. doi: 10.1016/s0140-6736(87)91728-4. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES