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. 1991 Aug;59(8):2609–2614. doi: 10.1128/iai.59.8.2609-2614.1991

Experimental elimination of tumor necrosis factor in low-dose endotoxin models has variable effects on survival.

A K Franks 1, K I Kujawa 1, L J Yaffe 1
PMCID: PMC258063  PMID: 1855980

Abstract

Tumor necrosis factor alpha (TNF) is thought to play a major role in the pathogenesis of septic shock. Anti-TNF antibody was preadministered in low-dose endotoxin lethality models in which BALB/c mice were challenged with small amounts of lipopolysaccharide following their sensitization with either carrageenan (CAR) or D-galactosamine (D-GalN). Although the antibody virtually eliminated circulating TNF in both the CAR and the D-GalN models, only the D-GalN model mice were afforded survival, adding to a growing body of evidence that substances other than TNF play a key role in endotoxin-induced lethality. Further examination of sera from these mice showed a much greater elevation of interleukin-6 levels in the CAR-sensitized group than in the D-GalN-sensitized group.

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Selected References

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  1. Aarden L. A., De Groot E. R., Schaap O. L., Lansdorp P. M. Production of hybridoma growth factor by human monocytes. Eur J Immunol. 1987 Oct;17(10):1411–1416. doi: 10.1002/eji.1830171004. [DOI] [PubMed] [Google Scholar]
  2. Allison A. C., Harington J. S., Birbeck M. An examination of the cytotoxic effects of silica on macrophages. J Exp Med. 1966 Aug 1;124(2):141–154. doi: 10.1084/jem.124.2.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BORSOS T., RAPP H. J., CRISLER C. THE INTERACTION BETWEEN CARRAGEENAN AND THE FIRST COMPONENT OF COMPLEMENT. J Immunol. 1965 May;94:662–666. [PubMed] [Google Scholar]
  4. Becker L. J., Rudbach J. A. Potentiation of endotoxicity by carrageenan. Infect Immun. 1978 Mar;19(3):1099–1100. doi: 10.1128/iai.19.3.1099-1100.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Beutler B. A., Milsark I. W., Cerami A. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo. J Immunol. 1985 Dec;135(6):3972–3977. [PubMed] [Google Scholar]
  6. 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]
  7. Brouckaert P., Spriggs D. R., Demetri G., Kufe D. W., Fiers W. Circulating interleukin 6 during a continuous infusion of tumor necrosis factor and interferon gamma. J Exp Med. 1989 Jun 1;169(6):2257–2262. doi: 10.1084/jem.169.6.2257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Catanzaro P. J., Schwartz H. J., Graham R. C., Jr Spectrum and possible mechanism of carrageenan cytotoxicity. Am J Pathol. 1971 Aug;64(2):387–404. [PMC free article] [PubMed] [Google Scholar]
  9. Cayphas S., Van Damme J., Vink A., Simpson R. J., Billiau A., Van Snick J. Identification of an interleukin HP1-like plasmacytoma growth factor produced by L cells in response to viral infection. J Immunol. 1987 Nov 1;139(9):2965–2969. [PubMed] [Google Scholar]
  10. Cross A. S., Sadoff J. C., Kelly N., Bernton E., Gemski P. Pretreatment with recombinant murine tumor necrosis factor alpha/cachectin and murine interleukin 1 alpha protects mice from lethal bacterial infection. J Exp Med. 1989 Jun 1;169(6):2021–2027. doi: 10.1084/jem.169.6.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feuerstein G., Hallenbeck J. M., Vanatta B., Rabinovici R., Perera P. Y., Vogel S. N. Effect of gram-negative endotoxin on levels of serum corticosterone, TNF alpha, circulating blood cells, and the survival of rats. Circ Shock. 1990 Mar;30(3):265–278. [PubMed] [Google Scholar]
  12. Flick D. A., Gifford G. E. Comparison of in vitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods. 1984 Mar 30;68(1-2):167–175. doi: 10.1016/0022-1759(84)90147-9. [DOI] [PubMed] [Google Scholar]
  13. Fong Y., Moldawer L. L., Marano M., Wei H., Tatter S. B., Clarick R. H., Santhanam U., Sherris D., May L. T., Sehgal P. B. Endotoxemia elicits increased circulating beta 2-IFN/IL-6 in man. J Immunol. 1989 Apr 1;142(7):2321–2324. [PubMed] [Google Scholar]
  14. Fong Y., Tracey K. J., Moldawer L. L., Hesse D. G., Manogue K. B., Kenney J. S., Lee A. T., Kuo G. C., Allison A. C., Lowry S. F. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp Med. 1989 Nov 1;170(5):1627–1633. doi: 10.1084/jem.170.5.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Freudenberg M. A., Galanos C. Induction of tolerance to lipopolysaccharide (LPS)-D-galactosamine lethality by pretreatment with LPS is mediated by macrophages. Infect Immun. 1988 May;56(5):1352–1357. doi: 10.1128/iai.56.5.1352-1357.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Freudenberg M. A., Keppler D., Galanos C. Requirement for lipopolysaccharide-responsive macrophages in galactosamine-induced sensitization to endotoxin. Infect Immun. 1986 Mar;51(3):891–895. doi: 10.1128/iai.51.3.891-895.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Galanos C., Freudenberg M. A., Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5939–5943. doi: 10.1073/pnas.76.11.5939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Helfgott D. C., May L. T., Sthoeger Z., Tamm I., Sehgal P. B. Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of beta 2 interferon by human fibroblasts. J Exp Med. 1987 Nov 1;166(5):1300–1309. doi: 10.1084/jem.166.5.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Helfgott D. C., Tatter S. B., Santhanam U., Clarick R. H., Bhardwaj N., May L. T., Sehgal P. B. Multiple forms of IFN-beta 2/IL-6 in serum and body fluids during acute bacterial infection. J Immunol. 1989 Feb 1;142(3):948–953. [PubMed] [Google Scholar]
  22. Jablons D. M., Mulé J. J., McIntosh J. K., Sehgal P. B., May L. T., Huang C. M., Rosenberg S. A., Lotze M. T. IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans. J Immunol. 1989 Mar 1;142(5):1542–1547. [PubMed] [Google Scholar]
  23. Jirik F. R., Podor T. J., Hirano T., Kishimoto T., Loskutoff D. J., Carson D. A., Lotz M. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol. 1989 Jan 1;142(1):144–147. [PubMed] [Google Scholar]
  24. Kaminski N. E., Holsapple M. P. Inhibition of macrophage accessory cell function in casein-treated B6C3F1 mice. J Immunol. 1987 Sep 15;139(6):1804–1810. [PubMed] [Google Scholar]
  25. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  26. 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]
  27. Nakajima K., Martínez-Maza O., Hirano T., Breen E. C., Nishanian P. G., Salazar-Gonzalez J. F., Fahey J. L., Kishimoto T. Induction of IL-6 (B cell stimulatory factor-2/IFN-beta 2) production by HIV. J Immunol. 1989 Jan 15;142(2):531–536. [PubMed] [Google Scholar]
  28. Ogata M., Yoshida S., Kamochi M., Shigematsu A., Mizuguchi Y. Enhancement of lipopolysaccharide-induced tumor necrosis factor production in mice by carrageenan pretreatment. Infect Immun. 1991 Feb;59(2):679–683. doi: 10.1128/iai.59.2.679-683.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Okuda Y., Hanazawa S. Comparison of the activation and interleukin-1 production of mouse peritoneal macrophages by three types of purified carrageenan. Josai Shika Daigaku Kiyo. 1986;15(3):557–566. [PubMed] [Google Scholar]
  30. Paul N. L., Ruddle N. H. Lymphotoxin. Annu Rev Immunol. 1988;6:407–438. doi: 10.1146/annurev.iy.06.040188.002203. [DOI] [PubMed] [Google Scholar]
  31. Schwartz H. J., Catanzaro P. J. The differential suppression of antigen, lymphokine and mitogen-induced delayed hypersensitivity-type skin reactions by carrageenan. Int Arch Allergy Appl Immunol. 1973;44(3):409–421. doi: 10.1159/000230948. [DOI] [PubMed] [Google Scholar]
  32. Schwartz H. J., Kellermeyer R. W. Carrageenan and delayed hypersensitivity. II. Activation of Hageman factor by carrageenan and its possible significance. Proc Soc Exp Biol Med. 1969 Dec;132(3):1021–1024. doi: 10.3181/00379727-132-34358. [DOI] [PubMed] [Google Scholar]
  33. Shalaby M. R., Waage A., Espevik T. Cytokine regulation of interleukin 6 production by human endothelial cells. Cell Immunol. 1989 Jul;121(2):372–382. doi: 10.1016/0008-8749(89)90036-1. [DOI] [PubMed] [Google Scholar]
  34. Starnes H. F., Jr, Pearce M. K., Tewari A., Yim J. H., Zou J. C., Abrams J. S. Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice. J Immunol. 1990 Dec 15;145(12):4185–4191. [PubMed] [Google Scholar]
  35. Suzuki F., Maeda H., Pollard R. B. Suppression of interferon gamma production in mice treated with carrageenan. Eur J Immunol. 1986 Apr;16(4):375–380. doi: 10.1002/eji.1830160411. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. 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]
  38. Tracey K. J., Lowry S. F., Cerami A. Cachectin: a hormone that triggers acute shock and chronic cachexia. J Infect Dis. 1988 Mar;157(3):413–420. doi: 10.1093/infdis/157.3.413. [DOI] [PubMed] [Google Scholar]
  39. Tracey K. J., Lowry S. F., Fahey T. J., 3rd, Albert J. D., Fong Y., Hesse D., Beutler B., Manogue K. R., Calvano S., Wei H. Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet. 1987 May;164(5):415–422. [PubMed] [Google Scholar]
  40. Van Snick J. Interleukin-6: an overview. Annu Rev Immunol. 1990;8:253–278. doi: 10.1146/annurev.iy.08.040190.001345. [DOI] [PubMed] [Google Scholar]
  41. Vijayakumar R. K., Muthukkaruppan V. R. Immunoregulatory processes induced by carrageenan in BALB/C mice. Immunol Invest. 1990 Apr;19(2):163–183. doi: 10.3109/08820139009042035. [DOI] [PubMed] [Google Scholar]
  42. Waage A., Espevik T. Interleukin 1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice. J Exp Med. 1988 Jun 1;167(6):1987–1992. doi: 10.1084/jem.167.6.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Wong G. G., Clark S. C. Multiple actions of interleukin 6 within a cytokine network. Immunol Today. 1988 May;9(5):137–139. doi: 10.1016/0167-5699(88)91200-5. [DOI] [PubMed] [Google Scholar]
  45. Zabel P., Wolter D. T., Schönharting M. M., Schade U. F. Oxpentifylline in endotoxaemia. Lancet. 1989 Dec 23;2(8678-8679):1474–1477. doi: 10.1016/s0140-6736(89)92929-2. [DOI] [PubMed] [Google Scholar]

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