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Clinical Immunology

Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria

Wilson L. Mandala, Chisomo L. Msefula, Esther N. Gondwe, Mark T. Drayson, Malcolm E. Molyneux, Calman A. MacLennan
David W. Pascual, Editor
Wilson L. Mandala
aMalawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi
bDepartment of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi
cLiverpool School of Tropical Medicine, Liverpool, United Kingdom
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Chisomo L. Msefula
aMalawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi
cLiverpool School of Tropical Medicine, Liverpool, United Kingdom
dDepartment of Microbiology, College of Medicine, University of Malawi, Blantyre, Malawi
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Esther N. Gondwe
aMalawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi
cLiverpool School of Tropical Medicine, Liverpool, United Kingdom
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Mark T. Drayson
eInstitute of Immunology and Immunotherapy, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
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Malcolm E. Molyneux
aMalawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi
cLiverpool School of Tropical Medicine, Liverpool, United Kingdom
fDepartment of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi
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Calman A. MacLennan
aMalawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi
eInstitute of Immunology and Immunotherapy, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
gThe Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
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David W. Pascual
University of Florida
Roles: Editor
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DOI: 10.1128/CVI.00533-16
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ABSTRACT

Proinflammatory cytokines are involved in clearance of Plasmodium 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.

FOOTNOTES

    • Received 13 December 2016.
    • Returned for modification 1 January 2017.
    • Accepted 18 January 2017.
    • Accepted manuscript posted online 25 January 2017.
  • Supplemental material for this article may be found at https://doi.org/10.1128/CVI.00533-16 .

  • Copyright © 2017 Mandala et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license .

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Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria
Wilson L. Mandala, Chisomo L. Msefula, Esther N. Gondwe, Mark T. Drayson, Malcolm E. Molyneux, Calman A. MacLennan
Clinical and Vaccine Immunology Apr 2017, 24 (4) e00533-16; DOI: 10.1128/CVI.00533-16

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Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria
Wilson L. Mandala, Chisomo L. Msefula, Esther N. Gondwe, Mark T. Drayson, Malcolm E. Molyneux, Calman A. MacLennan
Clinical and Vaccine Immunology Apr 2017, 24 (4) e00533-16; DOI: 10.1128/CVI.00533-16
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KEYWORDS

cytokines
Malaria, Falciparum
cytokines
malaria

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