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. 1998;7(5):339–346. doi: 10.1080/09629359890866

Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom.

S F Barros 1, I Friedlanskaia 1, V L Petricevich 1, T L Kipnis 1
PMCID: PMC1781860  PMID: 9883969

Abstract

We have provided evidence that: (a) lethality of mice to crude Bothrops venom varies according the isogenic strain (A/J > C57Bl/6 > A/Sn > BALB/c > C3H/HePas > DBA/2 > C3H/He); (b)BALB/c mice (LD50=100.0 microg) were injected i.p. with 50 microg of venom produced IL-6, IL-10, INF-gamma, TNF-alpha and NO in the serum. In vitro the cells from the mice injected and challenged with the venom only released IL-10 while peritoneal macrophages released IL-10, INF-gamma and less amounts of IL-6; (c) establishment of local inflammation and necrosis induced by the venom, coincides with the peaks of TNF-alpha, IFN-gamma and NO and the damage was neutralized when the venom was incubated with a monoclonal antibody against a 60 kDa haemorrhagic factor. These results suggest that susceptibility to Bothrops atrox venom is genetically dependent but MHC independent; that IL-6, IL-10, TNF-alpha, IFN-gamma and NO can be involved in the mediation of tissue damage; and that the major venom component inducers of the lesions are haemorrhagins.

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Selected References

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  1. Albelda S. M., Smith C. W., Ward P. A. Adhesion molecules and inflammatory injury. FASEB J. 1994 May;8(8):504–512. [PubMed] [Google Scholar]
  2. Amaral C. F., Rezende N. A., Pedrosa T. M., da Silva O. A., Pedroso E. R. Afibrinogenemia secundária a acidente ofídico crotálico. (Crotalus durissus terrificus). Rev Inst Med Trop Sao Paulo. 1988 Jul-Aug;30(4):288–292. doi: 10.1590/s0036-46651988000400007. [DOI] [PubMed] [Google Scholar]
  3. Amaral C. F., de Rezende N. A., da Silva O. A., Ribeiro M. M., Magalhães R. A., dos Reis R. J., Carneiro J. G., Castro J. R. Insuficiência renal aguda secundária a acidentes ofídicos botrópico e crotálico. Análise de 63 casos. Rev Inst Med Trop Sao Paulo. 1986 Jul-Aug;28(4):220–227. doi: 10.1590/s0036-46651986000400003. [DOI] [PubMed] [Google Scholar]
  4. Bacon K. B., Westwick J., Camp R. D. Potent and specific inhibition of IL-8-, IL-1 alpha- and IL-1 beta-induced in vitro human lymphocyte migration by calcium channel antagonists. Biochem Biophys Res Commun. 1989 Nov 30;165(1):349–354. doi: 10.1016/0006-291x(89)91076-0. [DOI] [PubMed] [Google Scholar]
  5. Butcher E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991 Dec 20;67(6):1033–1036. doi: 10.1016/0092-8674(91)90279-8. [DOI] [PubMed] [Google Scholar]
  6. Fiorentino D. F., Zlotnik A., Mosmann T. R., Howard M., O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol. 1991 Dec 1;147(11):3815–3822. [PubMed] [Google Scholar]
  7. Gazzinelli R. T., Oswald I. P., James S. L., Sher A. IL-10 inhibits parasite killing and nitrogen oxide production by IFN-gamma-activated macrophages. J Immunol. 1992 Mar 15;148(6):1792–1796. [PubMed] [Google Scholar]
  8. Howard M., Muchamuel T., Andrade S., Menon S. Interleukin 10 protects mice from lethal endotoxemia. J Exp Med. 1993 Apr 1;177(4):1205–1208. doi: 10.1084/jem.177.4.1205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Huber A. R., Kunkel S. L., Todd R. F., 3rd, Weiss S. J. Regulation of transendothelial neutrophil migration by endogenous interleukin-8. Science. 1991 Oct 4;254(5028):99–102. doi: 10.1126/science.1718038. [DOI] [PubMed] [Google Scholar]
  10. Larsen C. G., Anderson A. O., Appella E., Oppenheim J. J., Matsushima K. The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes. Science. 1989 Mar 17;243(4897):1464–1466. doi: 10.1126/science.2648569. [DOI] [PubMed] [Google Scholar]
  11. Leonard E. J., Skeel A., Yoshimura T., Noer K., Kutvirt S., Van Epps D. Leukocyte specificity and binding of human neutrophil attractant/activation protein-1. J Immunol. 1990 Feb 15;144(4):1323–1330. [PubMed] [Google Scholar]
  12. Lima M. R., dos Santos M. C., Tambourgi D. V., Marques T., da Silva W. D., Kipnis T. Susceptibility of different strains of mice to South American rattlesnake (Crotalus durissus terrificus) venom: correlation between lethal effect and creatine kinase release. Toxicon. 1991;29(6):783–786. doi: 10.1016/0041-0101(91)90070-8. [DOI] [PubMed] [Google Scholar]
  13. Lomonte B., Tarkowski A., Hanson L. A. Host response to Bothrops asper snake venom. Analysis of edema formation, inflammatory cells, and cytokine release in a mouse model. Inflammation. 1993 Apr;17(2):93–105. doi: 10.1007/BF00916097. [DOI] [PubMed] [Google Scholar]
  14. Mantovani A., Bussolino F., Introna M. Cytokine regulation of endothelial cell function: from molecular level to the bedside. Immunol Today. 1997 May;18(5):231–240. doi: 10.1016/s0167-5699(97)81662-3. [DOI] [PubMed] [Google Scholar]
  15. Moore K. W., O'Garra A., de Waal Malefyt R., Vieira P., Mosmann T. R. Interleukin-10. Annu Rev Immunol. 1993;11:165–190. doi: 10.1146/annurev.iy.11.040193.001121. [DOI] [PubMed] [Google Scholar]
  16. Moura-da-Silva A. M., Laing G. D., Paine M. J., Dennison J. M., Politi V., Crampton J. M., Theakston R. D. Processing of pro-tumor necrosis factor-alpha by venom metalloproteinases: a hypothesis explaining local tissue damage following snake bite. Eur J Immunol. 1996 Sep;26(9):2000–2005. doi: 10.1002/eji.1830260905. [DOI] [PubMed] [Google Scholar]
  17. Mulligan M. S., Smith C. W., Anderson D. C., Todd R. F., 3rd, Miyasaka M., Tamatani T., Issekutz T. B., Ward P. A. Role of leukocyte adhesion molecules in complement-induced lung injury. J Immunol. 1993 Mar 15;150(6):2401–2406. [PubMed] [Google Scholar]
  18. Ruff M. R., Gifford G. E. Purification and physico-chemical characterization of rabbit tumor necrosis factor. J Immunol. 1980 Oct;125(4):1671–1677. [PubMed] [Google Scholar]
  19. Schmidt H. H., Wilke P., Evers B., Böhme E. Enzymatic formation of nitrogen oxides from L-arginine in bovine brain cytosol. Biochem Biophys Res Commun. 1989 Nov 30;165(1):284–291. doi: 10.1016/0006-291x(89)91067-x. [DOI] [PubMed] [Google Scholar]
  20. Schumacher J. H., O'Garra A., Shrader B., van Kimmenade A., Bond M. W., Mosmann T. R., Coffman R. L. The characterization of four monoclonal antibodies specific for mouse IL-5 and development of mouse and human IL-5 enzyme-linked immunosorbent. J Immunol. 1988 Sep 1;141(5):1576–1581. [PubMed] [Google Scholar]
  21. Tambourgi D. V., dos Santos M. C., Furtado M. de F., de Freitas M. C., da Silva W. D., Kipnis T. L. Pro-inflammatory activities in elapid snake venoms. Br J Pharmacol. 1994 Jul;112(3):723–727. doi: 10.1111/j.1476-5381.1994.tb13137.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. da Silva W. D., Eisele J. W., Lepow I. H. Complement as a mediator of inflammation. 3. Purification of the activity with anaphylatoxin properties generated by interaction of the first four components of complement and its identification as a cleavage product of C'3. J Exp Med. 1967 Dec 1;126(6):1027–1048. doi: 10.1084/jem.126.6.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

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