title: Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria.
abstract: Proinflammatory cytokines are involved in clearance ofPlasmodium falciparum, and very high levels of these cytokines have been implicated in the pathogenesis of severe malaria. In order to determine how cytokines vary with disease severity and syndrome, we enrolled Malawian children presenting with cerebral malaria (CM), severe malarial anemia (SMA), and uncomplicated malaria (UCM) and healthy controls. We analyzed serum cytokine concentrations in acute infection and in convalescence. With the exception of interleukin 5 (IL-5), cytokine concentrations were highest in acute CM, followed by SMA, and were only mildly elevated in UCM. Cytokine concentrations had fallen to control levels when remeasured at 1 month of convalescence in all three clinical malaria groups. Ratios of IL-10 to tumor necrosis factor alpha (TNF-α) and of IL-10 to IL-6 followed a similar pattern. Children presenting with acute CM had significantly higher concentrations of TNF-α (P< 0.001), interferon gamma (IFN-γ) (P= 0.0019), IL-2 (P= 0.0004), IL-6 (P< 0.001), IL-8 (P< 0.001), and IL-10 (P< 0.001) in sera than healthy controls. Patients with acute CM had significantly higher concentrations of IL-6 (P< 0.001) and IL-10 (P= 0.0003) than those presenting with acute SMA. Our findings are consistent with the concept that high levels of proinflammatory cytokines, despite high levels of the anti-inflammatory cytokine IL-10, could contribute to the pathogenesis of CM.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi wmandala2002@gmail.com.|Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi.|Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Wilson L
authors.initials: WL
authors.lastname: Mandala
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.|Liverpool School of Tropical Medicine, Liverpool, United Kingdom.|Department of Microbiology, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Chisomo L
authors.initials: CL
authors.lastname: Msefula
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.|Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Esther N
authors.initials: EN
authors.lastname: Gondwe
authors.affiliation: Institute of Immunology and Immunotherapy, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Drayson
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.|Liverpool School of Tropical Medicine, Liverpool, United Kingdom.|Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.|Institute of Immunology and Immunotherapy, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.|The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Calman A
authors.initials: CA
authors.lastname: MacLennan
mesh_terms: D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D044967:Serum / Q000737:chemistry
chemical_list: D016207:Cytokines
keywords: cytokines; malaria