Evidence of IL-17, IP-10, and IL-10 involvement in multiple-organ dysfunction and IL-17 pathway in acute renal failure associated to Plasmodium falciparum malariaReportar como inadecuado




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Journal of Translational Medicine

, 13:369

Diseasebiomarkers

Abstract

BackgroundPlasmodium falciparum malaria in India is characterized by high rates of severe disease, with multiple organ dysfunction MOD—mainly associated with acute renal failure ARF—and increased mortality. The objective of this study is to identify cytokine signatures differentiating severe malaria patients with MOD, cerebral malaria CM, and cerebral malaria with MOD CM-MOD in India. We have previously shown that two cytokines clusters differentiated CM from mild malaria in Maharashtra. Hence, we also aimed to determine if these cytokines could discriminate malaria subphenotypes in Odisha.

MethodsP. falciparum malaria patients from the SCB Medical College Cuttack in the Odisha state in India were enrolled along with three sets of controls: healthy individuals, patients with sepsis and encephalitis n = 222. We determined plasma concentrations of pro- and anti-inflammatory cytokines and chemokines for all individuals using a multiplex assay. We then used an ensemble of statistical analytical methods to ascertain whether particular sets of cytokines-chemokines were predictors of severity or signatures of a disease category.

ResultsOf the 26 cytokines-chemokines tested, 19 increased significantly during malaria and clearly distinguished malaria patients from controls, as well as sepsis and encephalitis patients. High amounts of IL-17, IP-10, and IL-10 predicted MOD, decreased IL-17 and MIP-1α segregated CM-MOD from MOD, and increased IL-12p40 differentiated CM from CM-MOD. Most severe malaria patients with ARF exhibited high levels of IL-17.

ConclusionWe report distinct differences in cytokine production correlating with malarial disease severity in Odisha and Maharashtra populations in India. We show that CM, CM-MOD and MOD are clearly distinct malaria-associated pathologies. High amounts of IL-17, IP-10, and IL-10 were predictors of MOD; decreased IL-17 and MIP-1α separated CM-MOD from MOD; and increased IL-12p40 differentiated CM from CM-MOD. Data also suggest that the IL-17 pathway may contribute to malaria pathogenesis via different regulatory mechanisms and may represent an interesting target to mitigate the pathological processes in malaria-associated ARF.

KeywordsPlasmodium falciparum Severe malaria Cerebral malaria Acute-renal failure Malaria associated organ failure IL-17 Cytokines Biomarkers AbbreviationsCMcerebral malaria

MODmultiple organ dysfunction

CM-MODcerebral malaria with MOD

ARFacute renal failure

MMuncomplicated malaria

SNCMsevere non cerebral malaria

ECasymptomatic carriers

SEPTsepsis

ENCencephalitis

MDSmultidimensional scaling

SVDsingle value decomposition

Fabien Herbert, Nicolas Tchitchek and Devendra Bansal have contributed equally

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-015-0731-6 contains supplementary material, which is available to authorized users.

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Autor: Fabien Herbert - Nicolas Tchitchek - Devendra Bansal - Julien Jacques - Sulabha Pathak - Christophe Bécavin - Constantin F

Fuente: https://link.springer.com/



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