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. 1994 Oct;62(10):4374–4379. doi: 10.1128/iai.62.10.4374-4379.1994

Increased concentrations of interleukin-6 and interleukin-1 receptor antagonist and decreased concentrations of beta-2-glycoprotein I in Gambian children with cerebral malaria.

P H Jakobsen 1, V McKay 1, S D Morris-Jones 1, W McGuire 1, M B van Hensbroek 1, S Meisner 1, K Bendtzen 1, I Schousboe 1, I C Bygbjerg 1, B M Greenwood 1
PMCID: PMC303119  PMID: 7927698

Abstract

To investigate the pathogenic versus the protective role of cytokines and toxin-binding factors in Plasmodium falciparum infections, we measured the concentrations of tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, and IL-6, as well as soluble receptors of tumor necrosis factor and IL-6 (sIL-6R) in serum of Gambian children with cerebral malaria, mild or asymptomatic malaria, or other illnesses unrelated to malaria. Because cytokine secretion may be triggered by toxic structures containing phosphatidylinositol (PI), we also measured concentrations of anti-PI antibodies and the PI-binding serum protein beta-2-glycoprotein I. We found increased concentrations of IL-6, sIL-6R, IL-1ra, and some immunoglobulin M antibodies against PI in children with cerebral malaria, but those who died had decreased concentrations of beta-2-glycoprotein I. We conclude that increased concentrations of cytokines and soluble cytokine receptors represent a normal host response to P. falciparum infections but that excessive secretion of cytokines like IL-6 may predispose to cerebral malaria and a fatal outcome while beta-2-glycoprotein I may protect against a fatal outcome of cerebral malaria.

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Selected References

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  1. Bate C. A., Taverne J., Bootsma H. J., Mason R. C., Skalko N., Gregoriadis G., Playfair J. H. Antibodies against phosphatidylinositol and inositol monophosphate specifically inhibit tumour necrosis factor induction by malaria exoantigens. Immunology. 1992 May;76(1):35–41. [PMC free article] [PubMed] [Google Scholar]
  2. Bate C. A., Taverne J., Playfair J. H. Detoxified exoantigens and phosphatidylinositol derivatives inhibit tumor necrosis factor induction by malarial exoantigens. Infect Immun. 1992 May;60(5):1894–1901. doi: 10.1128/iai.60.5.1894-1901.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berendt A. R., Simmons D. L., Tansey J., Newbold C. I., Marsh K. Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum. Nature. 1989 Sep 7;341(6237):57–59. doi: 10.1038/341057a0. [DOI] [PubMed] [Google Scholar]
  4. Blick M., Sherwin S. A., Rosenblum M., Gutterman J. Phase I study of recombinant tumor necrosis factor in cancer patients. Cancer Res. 1987 Jun 1;47(11):2986–2989. [PubMed] [Google Scholar]
  5. Grassi J., Roberge C. J., Frobert Y., Pradelles P., Poubelle P. E. Determination of IL1 alpha, IL1 beta and IL2 in biological media using specific enzyme immunometric assays. Immunol Rev. 1991 Feb;119:125–145. doi: 10.1111/j.1600-065x.1991.tb00581.x. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. 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]
  9. Greenwood B. M., Armstrong J. R. Comparison of two simple methods for determining malaria parasite density. Trans R Soc Trop Med Hyg. 1991 Mar-Apr;85(2):186–188. doi: 10.1016/0035-9203(91)90015-q. [DOI] [PubMed] [Google Scholar]
  10. Greenwood B., Marsh K., Snow R. Why do some African children develop severe malaria? Parasitol Today. 1991 Oct;7(10):277–281. doi: 10.1016/0169-4758(91)90096-7. [DOI] [PubMed] [Google Scholar]
  11. Hansen M. B., Svenson M., Bendtzen K. Human anti-interleukin 1 alpha antibodies. Immunol Lett. 1991 Sep;30(1):133–139. doi: 10.1016/0165-2478(91)90102-g. [DOI] [PubMed] [Google Scholar]
  12. Hansen M. B., Svenson M., Diamant M., Bendtzen K. Anti-interleukin-6 antibodies in normal human serum. Scand J Immunol. 1991 Jun;33(6):777–781. doi: 10.1111/j.1365-3083.1991.tb02552.x. [DOI] [PubMed] [Google Scholar]
  13. Hunt J. E., McNeil H. P., Morgan G. J., Crameri R. M., Krilis S. A. A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection. Lupus. 1992 Feb;1(2):75–81. doi: 10.1177/096120339200100204. [DOI] [PubMed] [Google Scholar]
  14. Jakobsen P. H., Moon R., Ridley R. G., Bate C. A., Taverne J., Hansen M. B., Takacs B., Playfair J. H., McBride J. S. Tumour necrosis factor and interleukin-6 production induced by components associated with merozoite proteins of Plasmodium falciparum. Parasite Immunol. 1993 Apr;15(4):229–237. doi: 10.1111/j.1365-3024.1993.tb00605.x. [DOI] [PubMed] [Google Scholar]
  15. Jakobsen P. H., Morris-Jones S. D., Hviid L., Theander T. G., Høier-Madsen M., Bayoumi R. A., Greenwood B. M. Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria. Immunology. 1993 Aug;79(4):653–657. [PMC free article] [PubMed] [Google Scholar]
  16. Kern P., Hemmer C. J., Gallati H., Neifer S., Kremsner P., Dietrich M., Porzsolt F. Soluble tumor necrosis factor receptors correlate with parasitemia and disease severity in human malaria. J Infect Dis. 1992 Oct;166(4):930–934. doi: 10.1093/infdis/166.4.930. [DOI] [PubMed] [Google Scholar]
  17. Kern P., Hemmer C. J., Van Damme J., Gruss H. J., Dietrich M. Elevated tumor necrosis factor alpha and interleukin-6 serum levels as markers for complicated Plasmodium falciparum malaria. Am J Med. 1989 Aug;87(2):139–143. doi: 10.1016/s0002-9343(89)80688-6. [DOI] [PubMed] [Google Scholar]
  18. Kumaratilake L. M., Ferrante A., Rzepczyk C. The role of T lymphocytes in immunity to Plasmodium falciparum. Enhancement of neutrophil-mediated parasite killing by lymphotoxin and IFN-gamma: comparisons with tumor necrosis factor effects. J Immunol. 1991 Jan 15;146(2):762–767. [PubMed] [Google Scholar]
  19. Kwiatkowski D. Febrile temperatures can synchronize the growth of Plasmodium falciparum in vitro. J Exp Med. 1989 Jan 1;169(1):357–361. doi: 10.1084/jem.169.1.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kwiatkowski D., Hill A. V., Sambou I., Twumasi P., Castracane J., Manogue K. R., Cerami A., Brewster D. R., Greenwood B. M. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet. 1990 Nov 17;336(8725):1201–1204. doi: 10.1016/0140-6736(90)92827-5. [DOI] [PubMed] [Google Scholar]
  21. Molyneux M. E., Taylor T. E., Wirima J. J., Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med. 1989 May;71(265):441–459. [PubMed] [Google Scholar]
  22. Pfeffer K., Matsuyama T., Kündig T. M., Wakeham A., Kishihara K., Shahinian A., Wiegmann K., Ohashi P. S., Krönke M., Mak T. W. Mice deficient for the 55 kd tumor necrosis factor receptor are resistant to endotoxic shock, yet succumb to L. monocytogenes infection. Cell. 1993 May 7;73(3):457–467. doi: 10.1016/0092-8674(93)90134-c. [DOI] [PubMed] [Google Scholar]
  23. Riley E. M., Jakobsen P. H., Allen S. J., Wheeler J. G., Bennett S., Jepsen S., Greenwood B. M. Immune response to soluble exoantigens of Plasmodium falciparum may contribute to both pathogenesis and protection in clinical malaria: evidence from a longitudinal, prospective study of semi-immune African children. Eur J Immunol. 1991 Apr;21(4):1019–1025. doi: 10.1002/eji.1830210424. [DOI] [PubMed] [Google Scholar]
  24. Schofield L., Hackett F. Signal transduction in host cells by a glycosylphosphatidylinositol toxin of malaria parasites. J Exp Med. 1993 Jan 1;177(1):145–153. doi: 10.1084/jem.177.1.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schousboe I. Addition of deoxycholate in electroimmunoassay and crossed immunofocusing for quantification of beta 2-glycoprotein I and its subfractions. J Biochem Biophys Methods. 1982 Jun;6(2):105–114. doi: 10.1016/0165-022x(82)90056-2. [DOI] [PubMed] [Google Scholar]
  26. Schousboe I. Characterization of the interaction between beta 2-glycoprotein I and mitochondria, platelets, liposomes and bile acids. Int J Biochem. 1983;15(12):1393–1401. doi: 10.1016/0020-711x(83)90070-8. [DOI] [PubMed] [Google Scholar]
  27. Schousboe I. Purification, characterization and identification of an agglutinin in human serum. Biochim Biophys Acta. 1979 Aug 28;579(2):396–408. doi: 10.1016/0005-2795(79)90067-9. [DOI] [PubMed] [Google Scholar]
  28. Shaffer N., Grau G. E., Hedberg K., Davachi F., Lyamba B., Hightower A. W., Breman J. G., Phuc N. D. Tumor necrosis factor and severe malaria. J Infect Dis. 1991 Jan;163(1):96–101. doi: 10.1093/infdis/163.1.96. [DOI] [PubMed] [Google Scholar]

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