Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Nov 1;172(5):1287–1291. doi: 10.1084/jem.172.5.1287

Low dosages of interleukin 1 protect mice against lethal cerebral malaria

PMCID: PMC2188656  PMID: 2230643

Abstract

In cerebral malaria, pathological changes can be found in the brain of infected people and in the brain of Plasmodium berghei-infected mice. The pathogenesis of cerebral malaria in mice is believed to be due to an immunopathological reaction giving rise to an excessive production of cytokines such as interferon gamma (IFN-gamma) and tumor necrosis factor (TNF). We find that low doses of interleukin 1 (IL-1) protect mice against cerebral malaria; IL-1 also inhibits parasitemia. The IL-1 effect on parasitemia was not observed in nude mice and was at least partly reversed in mice treated with IL-1 in combination with antibody to IFN-gamma, indicating the involvement of T cells. Mice protected against development of cerebral malaria by IL-1 treatment developed the syndrome when TNF was given as observed in control infected mice or infected mice treated with inactivated IL-1.

Full Text

The Full Text of this article is available as a PDF (514.0 KB).

Selected References

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

  1. Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  2. Clark I. A., Cowden W. B., Butcher G. A., Hunt N. H. Possible roles of tumor necrosis factor in the pathology of malaria. Am J Pathol. 1987 Oct;129(1):192–199. [PMC free article] [PubMed] [Google Scholar]
  3. Clark I. A., Hunt N. H., Butcher G. A., Cowden W. B. Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-gamma or tumor necrosis factor, and its enhancement by butylated hydroxyanisole. J Immunol. 1987 Nov 15;139(10):3493–3496. [PubMed] [Google Scholar]
  4. Clark I. A. Monokines and lymphokines in malarial pathology. Ann Trop Med Parasitol. 1987 Oct;81(5):577–585. doi: 10.1080/00034983.1987.11812159. [DOI] [PubMed] [Google Scholar]
  5. Curfs J. H., Schetters T. P., Hermsen C. C., Jerusalem C. R., van Zon A. A., Eling W. M. Immunological aspects of cerebral lesions in murine malaria. Clin Exp Immunol. 1989 Jan;75(1):136–140. [PMC free article] [PubMed] [Google Scholar]
  6. Czuprynski C. J., Brown J. F. Recombinant murine interleukin-1 alpha enhancement of nonspecific antibacterial resistance. Infect Immun. 1987 Sep;55(9):2061–2065. doi: 10.1128/iai.55.9.2061-2065.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grau G. E., Kindler V., Piguet P. F., Lambert P. H., Vassalli P. Prevention of experimental cerebral malaria by anticytokine antibodies. Interleukin 3 and granulocyte macrophage colony-stimulating factor are intermediates in increased tumor necrosis factor production and macrophage accumulation. J Exp Med. 1988 Oct 1;168(4):1499–1504. doi: 10.1084/jem.168.4.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Grau G. E., Piguet P. F., Engers H. D., Louis J. A., Vassalli P., Lambert P. H. L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria. J Immunol. 1986 Oct 1;137(7):2348–2354. [PubMed] [Google Scholar]
  9. Hejna J. M., Rencricca N. J., Coleman R. M. Effective recovery and immunity to virulent malaria following red cell transfusion at crisis. Proc Soc Exp Biol Med. 1974 Jun;146(2):462–464. doi: 10.3181/00379727-146-38126. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Ozaki Y., Ohashi T., Minami A., Nakamura S. Enhanced resistance of mice to bacterial infection induced by recombinant human interleukin-1a. Infect Immun. 1987 Jun;55(6):1436–1440. doi: 10.1128/iai.55.6.1436-1440.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rest J. R. Cerebral malaria in inbred mice. I. A new model and its pathology. Trans R Soc Trop Med Hyg. 1982;76(3):410–415. doi: 10.1016/0035-9203(82)90203-6. [DOI] [PubMed] [Google Scholar]
  13. Schooley J. C., Kullgren B., Allison A. C. Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. Br J Haematol. 1987 Sep;67(1):11–17. doi: 10.1111/j.1365-2141.1987.tb02289.x. [DOI] [PubMed] [Google Scholar]
  14. Van't Wout J. W., Van der Meer J. W., Barza M., Dinarello C. A. Protection of neutropenic mice from lethal Candida albicans infection by recombinant interleukin 1. Eur J Immunol. 1988 Jul;18(7):1143–1146. doi: 10.1002/eji.1830180728. [DOI] [PubMed] [Google Scholar]
  15. Wallach D., Holtmann H., Engelmann H., Nophar Y. Sensitization and desensitization to lethal effects of tumor necrosis factor and IL-1. J Immunol. 1988 May 1;140(9):2994–2999. [PubMed] [Google Scholar]
  16. Wright D. H., Masembe R. M., Bazira E. R. The effect of antithymocyte serum on golden hamsters and rats infected with Plasmodium berghei. Br J Exp Pathol. 1971 Oct;52(5):465–477. [PMC free article] [PubMed] [Google Scholar]
  17. van der Meer J. W., Barza M., Wolff S. M., Dinarello C. A. A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1620–1623. doi: 10.1073/pnas.85.5.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. van der Meer J. W. The effects of recombinant interleukin-1 and recombinant tumor necrosis factor on non-specific resistance to infection. Biotherapy. 1988;1(1):19–25. doi: 10.1007/BF02170132. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES