title: Experimental cerebral malaria: possible new mechanisms in the TNF-induced microvascular pathology.
abstract: In order to contribute to the prevention of malaria morbidity and mortality, especially in endemic zones, we have carried out a series of studies on cytokine interactions in an experimental model of cerebral malaria (CM). This rapidly lethal syndrome develops, in some strains of mice, upon infection with Plasmodium berghei ANKA (PbA). A crucial mediator of neurovascular lesions appears to be TNF, found in high amounts in relation with cerebral complications, in both experimental and human CM. In experimental CM, in vivo injections of anti-cytokine antibodies have been used to analyze the cascade of reactions leading to brain vascular damage. In this review, we fill focus on the interplay of cytokines responsible for TNF overproduction in experimental malaria, therefore delineating the subset of T cells whose activation can lead to pathology, and effector mechanisms of neurovascular lesions characteristic of mouse cerebral malaria, with recent findings that appear to involve an unexpected cell type, the blood platelet.
authors.affiliation: WHO-IRTC, Department of Pathology, Faculty of Medicine, University of Geneva.
authors.forename: G E
authors.initials: GE
authors.lastname: Grau
authors.forename: J N
authors.initials: JN
authors.lastname: Lou
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000276:immunology; D015415:Biomarkers; D001792:Blood Platelets / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D016779:Malaria, Cerebral / Q000378:metabolism / Q000469:parasitology / Q000473:pathology*; D051379:Mice; D008833:Microcirculation / Q000648:ultrastructure; D010962:Plasmodium berghei; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D015415:Biomarkers; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha