title: Cerebral malaria: gamma-interferon redux.
abstract: There are two theories that seek to explain the pathogenesis of cerebral malaria, the mechanical obstruction hypothesis and the immunopathology hypothesis. Evidence consistent with both ideas has accumulated from studies of the human disease and experimental models. Thus, some combination of these concepts seems necessary to explain the very complex pattern of changes seen in cerebral malaria. The interactions between malaria parasites, erythrocytes, the cerebral microvascular endothelium, brain parenchymal cells, platelets and microparticles need to be considered. One factor that seems able to knit together much of this complexity is the cytokine interferon-gamma (IFN-γ). In this review we consider findings from the clinical disease, in vitro models and the murine counterpart of human cerebral malaria in order to evaluate the roles played by IFN-γ in the pathogenesis of this often fatal and debilitating condition.
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Hunt
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Ball
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Hansen
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Loke T
authors.initials: LT
authors.lastname: Khaw
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Jintao
authors.initials: J
authors.lastname: Guo
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Supun
authors.initials: S
authors.lastname: Bakmiwewa
authors.affiliation: Molecular Immunopathology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Mitchell
authors.affiliation: Vascular Immunology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Valéry
authors.initials: V
authors.lastname: Combes
authors.affiliation: Vascular Immunology Unit, School of Medical Sciences and Bosch Institute, University of Sydney Sydney, NSW, Australia.
authors.forename: Georges E R
authors.initials: GE
authors.lastname: Grau
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D016779:Malaria, Cerebral / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D007371:Interferon-gamma
keywords: CD8+T lymphocyte; blood-brain barrier; cerebral malaria; immunopathology; interferon-gamma; kynurenine pathway; microparticles; platelets