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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 malaria

BACKGROUND: Plasmodium 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 m...

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Autores principales: Herbert, Fabien, Tchitchek, Nicolas, Bansal, Devendra, Jacques, Julien, Pathak, Sulabha, Bécavin, Christophe, Fesel, Constantin, Dalko, Esther, Cazenave, Pierre-André, Preda, Cristian, Ravindran, Balachandran, Sharma, Shobhona, Das, Bidyut, Pied, Sylviane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658812/
https://www.ncbi.nlm.nih.gov/pubmed/26602091
http://dx.doi.org/10.1186/s12967-015-0731-6
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author Herbert, Fabien
Tchitchek, Nicolas
Bansal, Devendra
Jacques, Julien
Pathak, Sulabha
Bécavin, Christophe
Fesel, Constantin
Dalko, Esther
Cazenave, Pierre-André
Preda, Cristian
Ravindran, Balachandran
Sharma, Shobhona
Das, Bidyut
Pied, Sylviane
author_facet Herbert, Fabien
Tchitchek, Nicolas
Bansal, Devendra
Jacques, Julien
Pathak, Sulabha
Bécavin, Christophe
Fesel, Constantin
Dalko, Esther
Cazenave, Pierre-André
Preda, Cristian
Ravindran, Balachandran
Sharma, Shobhona
Das, Bidyut
Pied, Sylviane
author_sort Herbert, Fabien
collection PubMed
description BACKGROUND: Plasmodium 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. METHODS: P. 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. RESULTS: Of 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. CONCLUSION: We 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The 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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spelling pubmed-46588122015-11-26 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 malaria Herbert, Fabien Tchitchek, Nicolas Bansal, Devendra Jacques, Julien Pathak, Sulabha Bécavin, Christophe Fesel, Constantin Dalko, Esther Cazenave, Pierre-André Preda, Cristian Ravindran, Balachandran Sharma, Shobhona Das, Bidyut Pied, Sylviane J Transl Med Research BACKGROUND: Plasmodium 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. METHODS: P. 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. RESULTS: Of 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. CONCLUSION: We 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-015-0731-6) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-24 /pmc/articles/PMC4658812/ /pubmed/26602091 http://dx.doi.org/10.1186/s12967-015-0731-6 Text en © Herbert et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Herbert, Fabien
Tchitchek, Nicolas
Bansal, Devendra
Jacques, Julien
Pathak, Sulabha
Bécavin, Christophe
Fesel, Constantin
Dalko, Esther
Cazenave, Pierre-André
Preda, Cristian
Ravindran, Balachandran
Sharma, Shobhona
Das, Bidyut
Pied, Sylviane
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 malaria
title 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 malaria
title_full 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 malaria
title_fullStr 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 malaria
title_full_unstemmed 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 malaria
title_short 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 malaria
title_sort 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 malaria
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4658812/
https://www.ncbi.nlm.nih.gov/pubmed/26602091
http://dx.doi.org/10.1186/s12967-015-0731-6
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