Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26602091
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
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
#MMPMID26602091
Herbert F
; Tchitchek N
; Bansal D
; Jacques J
; Pathak S
; Bécavin C
; Fesel C
; Dalko E
; Cazenave PA
; Preda C
; Ravindran B
; Sharma S
; Das B
; Pied S
J Transl Med
2015[Nov]; 13
(?): 369
PMID26602091
show ga
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-1? 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-1? 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.
free
free
free
