title: Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium falciparum malaria.
abstract: The relationship between malaria-related outcomes and cytokine production in whole blood cultures associated with cellular immune responses and immunity to Plasmodium falciparum malaria was examined in a study in southern Ghana. Production of malaria-specific interferon (IFN)-gamma was associated with reduced risk of fever and clinical malaria. Protective IFN-gamma responses were induced by live schizonts but not by dead parasites. Production of malaria-specific tumor necrosis factor (TNF)-alpha was associated with reduced risk of fever during follow-up. Baseline levels of TNF-alpha and phytohemagglutinin (PHA)-induced interleukin (IL)-10 were positively associated with hemoglobin concentration. IL-12 production was associated with reduced risk of parasitemia. PHA-induced transforming growth factor-beta production was associated with reduced risk of fever during follow-up. High ratios of proinflammatory to anti-inflammatory cytokines were associated with increased risk of fever and higher hemoglobin concentrations. Thus, absolute levels and ratios of proinflammatory and anti-inflammatory cytokines influence susceptibility to infection, clinical disease, and anemia. These data contradict data from cross-sectional clinical studies and indicate a need for detailed analysis of the relationship between cellular immunity to malaria and resistance to disease.
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
authors.forename: D
authors.initials: D
authors.lastname: Dodoo
authors.forename: F M
authors.initials: FM
authors.lastname: Omer
authors.forename: J
authors.initials: J
authors.lastname: Todd
authors.forename: B D
authors.initials: BD
authors.lastname: Akanmori
authors.forename: K A
authors.initials: KA
authors.lastname: Koram
authors.forename: E M
authors.initials: EM
authors.lastname: Riley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001773:Blood Cells / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007109:Immunity; D007223:Infant; D007249:Inflammation / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D011237:Predictive Value of Tests
chemical_list: D016207:Cytokines