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Infect Immun. 1997 Nov; 65(11): 4883–4887.
doi: 10.1128/iai.65.11.4883-4887.1997
PMCID: PMC175703
PMID: 9353082

Cytokine profile suggesting that murine cerebral malaria is an encephalitis.

V M Jennings, J K Actor, A A Lal, and R L Hunter
Author information Copyright and License information PMC Disclaimer

Abstract

Cerebral malaria (CM) remains a poorly understood and life-threatening complication of malaria caused by the parasite Plasmodium falciparum. The discovery that murine CM caused by Plasmodium berghei ANKA and human CM are both characterized by production of inflammatory cytokines, especially tumor necrosis factor alpha (TNF-alpha), led to a revival of the suggestion that P. berghei CM may have value as a model of the human disease. In this study, quantitative reverse transcription-PCR was used to measure levels of message for 18S rRNA of P. berghei and 10 cytokines in the brains, livers, and spleens of mice during the induction and course of CM. A coordinated increase in RNA of parasite and proinflammatory cytokines was observed in the brains of mice in parallel with onset of CM. Levels of message for parasite, TNF-alpha, and gamma interferon increased in the brains of mice from day 5 to death on day 7. These changes were observed only in the brain, and message for other cytokines remained near baseline levels. This demonstrated that parasite sequestration does take place in the brains of mice with CM. Histologically, CM was characterized by widespread damage to the microvasculature in the brain with focal infiltration of inflammatory cells. The pattern of cytokine production in the brain is characteristic of other murine encephalitides.

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Selected References

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  • Aikawa M. Human cerebral malaria. Am J Trop Med Hyg. 1988 Jul;39(1):3–10. [PubMed] [Google Scholar]
  • Barnwell JW, Howard RJ, Coon HG, Miller LH. Splenic requirement for antigenic variation and expression of the variant antigen on the erythrocyte membrane in cloned Plasmodium knowlesi malaria. Infect Immun. 1983 Jun;40(3):985–994. [PMC free article] [PubMed] [Google Scholar]
  • Berman JW, Guida MP, Warren J, Amat J, Brosnan CF. Localization of monocyte chemoattractant peptide-1 expression in the central nervous system in experimental autoimmune encephalomyelitis and trauma in the rat. J Immunol. 1996 Apr 15;156(8):3017–3023. [PubMed] [Google Scholar]
  • Boonpucknavig V, Boonpucknavig S, Udomsangpetch R, Nitiyanant P. An immunofluorescence study of cerebral malaria. A correlation with histopathology. Arch Pathol Lab Med. 1990 Oct;114(10):1028–1034. [PubMed] [Google Scholar]
  • Campbell IL, Hobbs MV, Kemper P, Oldstone MB. Cerebral expression of multiple cytokine genes in mice with lymphocytic choriomeningitis. J Immunol. 1994 Jan 15;152(2):716–723. [PubMed] [Google Scholar]
  • Clark IA, Ilschner S, MacMicking JD, Cowden WB. TNF and Plasmodium berghei ANKA-induced cerebral malaria. Immunol Lett. 1990 Aug;25(1-3):195–198. [PubMed] [Google Scholar]
  • Claudio L, Martiney JA, Brosnan CF. Ultrastructural studies of the blood-retina barrier after exposure to interleukin-1 beta or tumor necrosis factor-alpha. Lab Invest. 1994 Jun;70(6):850–861. [PubMed] [Google Scholar]
  • Corsini E, Dufour A, Ciusani E, Gelati M, Frigerio S, Gritti A, Cajola L, Mancardi GL, Massa G, Salmaggi A. Human brain endothelial cells and astrocytes produce IL-1 beta but not IL-10. Scand J Immunol. 1996 Nov;44(5):506–511. [PubMed] [Google Scholar]
  • de Kossodo S, Grau GE. Profiles of cytokine production in relation with susceptibility to cerebral malaria. J Immunol. 1993 Nov 1;151(9):4811–4820. [PubMed] [Google Scholar]
  • de Kossodo S, Grau GE. Role of cytokines and adhesion molecules in malaria immunopathology. Stem Cells. 1993 Jan;11(1):41–48. [PubMed] [Google Scholar]
  • Elfont RM, Griffin DE, Goldstein GW. Enhanced endothelial cell adhesion of human cerebrospinal fluid lymphocytes. Ann Neurol. 1995 Sep;38(3):405–413. [PubMed] [Google Scholar]
  • Grau GE. Essential role of tumor necrosis factor and other cytokines in the pathogenesis of cerebral malaria: experimental and clinical studies. Verh K Acad Geneeskd Belg. 1992;54(2):155–175. [PubMed] [Google Scholar]
  • Grau GE, Fajardo LF, Piguet PF, Allet B, Lambert PH, Vassalli P. Tumor necrosis factor (cachectin) as an essential mediator in murine cerebral malaria. Science. 1987 Sep 4;237(4819):1210–1212. [PubMed] [Google Scholar]
  • Grau GE, Lou JN. Experimental cerebral malaria: possible new mechanisms in the TNF-induced microvascular pathology. Soz Praventivmed. 1995;40(1):50–57. [PubMed] [Google Scholar]
  • Grau GE, Taylor TE, Molyneux ME, Wirima JJ, Vassalli P, Hommel M, Lambert PH. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med. 1989 Jun 15;320(24):1586–1591. [PubMed] [Google Scholar]
  • Jakobsen PH, Bate CA, Taverne J, Playfair JH. Malaria: toxins, cytokines and disease. Parasite Immunol. 1995 May;17(5):223–231. [PubMed] [Google Scholar]
  • Kern P, Hemmer CJ, 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. [PubMed] [Google Scholar]
  • Lafortune L, Nalbantoglu J, Antel JP. Expression of tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) mRNA in adult human astrocytes: comparison with adult microglia and fetal astrocytes. J Neuropathol Exp Neurol. 1996 May;55(5):515–521. [PubMed] [Google Scholar]
  • Mabeza GF, Moyo VM, Thuma PE, Biemba G, Parry D, Khumalo H, Nyarugwe P, Zulu S, Gordeuk VR. Predictors of severity of illness on presentation in children with cerebral malaria. Ann Trop Med Parasitol. 1995 Jun;89(3):221–228. [PubMed] [Google Scholar]
  • MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol. 1985 Jun;119(3):385–401. [PMC free article] [PubMed] [Google Scholar]
  • McGuire W, Hill AV, Allsopp CE, Greenwood BM, Kwiatkowski D. Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria. Nature. 1994 Oct 6;371(6497):508–510. [PubMed] [Google Scholar]
  • Molyneux ME, Engelmann H, Taylor TE, Wirima JJ, Aderka D, Wallach D, Grau GE. Circulating plasma receptors for tumour necrosis factor in Malawian children with severe falciparum malaria. Cytokine. 1993 Nov;5(6):604–609. [PubMed] [Google Scholar]
  • Okuda Y, Nakatsuji Y, Fujimura H, Esumi H, Ogura T, Yanagihara T, Sakoda S. Expression of the inducible isoform of nitric oxide synthase in the central nervous system of mice correlates with the severity of actively induced experimental allergic encephalomyelitis. J Neuroimmunol. 1995 Oct;62(1):103–112. [PubMed] [Google Scholar]
  • Patnaik JK, Das BS, Mishra SK, Mohanty S, Satpathy SK, Mohanty D. Vascular clogging, mononuclear cell margination, and enhanced vascular permeability in the pathogenesis of human cerebral malaria. Am J Trop Med Hyg. 1994 Nov;51(5):642–647. [PubMed] [Google Scholar]
  • Polder T, Jerusalem C, Eling W. Topographical distribution of the cerebral lesions in mice infected with Plasmodium berghei. Tropenmed Parasitol. 1983 Dec;34(4):235–243. [PubMed] [Google Scholar]
  • Polder TW, Jerusalem CR, Eling WM. Morphological characteristics of intracerebral arterioles in clinical (Plasmodium falciparum) and experimental (Plasmodium berghei) cerebral malaria. J Neurol Sci. 1991 Jan;101(1):35–46. [PubMed] [Google Scholar]
  • Porta J, Carota A, Pizzolato GP, Wildi E, Widmer MC, Margairaz C, Grau GE. Immunopathological changes in human cerebral malaria. Clin Neuropathol. 1993 May-Jun;12(3):142–146. [PubMed] [Google Scholar]
  • Renno T, Lin JY, Piccirillo C, Antel J, Owens T. Cytokine production by cells in cerebrospinal fluid during experimental allergic encephalomyelitis in SJL/J mice. J Neuroimmunol. 1994 Jan;49(1-2):1–7. [PubMed] [Google Scholar]
  • Riganti M, Pongponratn E, Tegoshi T, Looareesuwan S, Punpoowong B, Aikawa M. Human cerebral malaria in Thailand: a clinico-pathological correlation. Immunol Lett. 1990 Aug;25(1-3):199–205. [PubMed] [Google Scholar]
  • Rudin W, Favre N, Bordmann G, Ryffel B. Interferon-gamma is essential for the development of cerebral malaria. Eur J Immunol. 1997 Apr;27(4):810–815. [PubMed] [Google Scholar]
  • Siddiqi AM, Jennings VM, Kidd MR, Actor JK, Hunter RL. Evaluation of electrochemiluminescence- and bioluminescence-based assays for quantitating specific DNA. J Clin Lab Anal. 1996;10(6):423–431. [PubMed] [Google Scholar]
  • Svetić A, Finkelman FD, Jian YC, Dieffenbach CW, Scott DE, McCarthy KF, Steinberg AD, Gause WC. Cytokine gene expression after in vivo primary immunization with goat antibody to mouse IgD antibody. J Immunol. 1991 Oct 1;147(7):2391–2397. [PubMed] [Google Scholar]
  • Toro G, Román G. Cerebral malaria. A disseminated vasculomyelinopathy. Arch Neurol. 1978 May;35(5):271–275. [PubMed] [Google Scholar]
  • Turner GD, Morrison H, Jones M, Davis TM, Looareesuwan S, Buley ID, Gatter KC, Newbold CI, Pukritayakamee S, Nagachinta B, et al. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994 Nov;145(5):1057–1069. [PMC free article] [PubMed] [Google Scholar]
  • Wynn TA, Eltoum I, Cheever AW, Lewis FA, Gause WC, Sher A. Analysis of cytokine mRNA expression during primary granuloma formation induced by eggs of Schistosoma mansoni. J Immunol. 1993 Aug 1;151(3):1430–1440. [PubMed] [Google Scholar]
  • Yoeli M. Chadwick lecture. Cerebral malaria--the quest for suitable experimental models in parasitic diseases of man. Trans R Soc Trop Med Hyg. 1976;70(1):24–35. [PubMed] [Google Scholar]
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