title: Dysregulation of cytokines expression in complicated falciparum malaria with increased TGF-β and IFN-γ and decreased IL-2 and IL-12.
abstract: BACKGROUND
  In Plasmodium falciparum infections, proinflammatory cytokine response is implicated in control of parasite multiplication as well as in disease pathogenesis. However, the regulation of proinflammatory and anti-inflammatory cytokine balance and its relation to disease severity remains poorly understood.
  
  
  METHODS
  We examined cytokines gene expression by quantitative real time-PCR technique in a case control study comprising of P. falciparum infected (n=58) and non infected (n=30) groups. P. falciparum infected were further stratified as complicated and uncomplicated as per WHO criterion and parasitaemia levels.
  
  
  RESULTS
  Higher expression of IL-2, IL-12α and TGF-β with decreased levels of IL-10 was seen in P. falciparum positivity. Complicated malaria was associated with enhanced expression of IFN-γ and TGF-β but lower IL-2 and IL-12α in comparison to uncomplicated malaria. Modeling of data suggested higher expression of IL-12α to be predictive of uncomplicated malaria [Odds ratio=3.074, 95% CI (1.254-7.536)] and was negatively associated with complicated malaria outcome (p=0.014). Interestingly, the probability of complicated malaria in males with elevated TNF-α expression was three times higher [p=0.05; Odds ratio=3.412, 95% CI (0.98-11.848)]. Age was also seen to be a factor with higher IL-8 in diseased young (p=0.012).
  
  
  CONCLUSIONS
  Our data suggested induction of balanced cytokine response in uncomplicated malaria while cytokine dysregulation with a role for TGF-β was indicated in complicated malaria. TH cells did not appear to be the source of increased IFN-γ expression associated with malaria severity.
authors.affiliation: Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam, India. Electronic address: sonialourembam@gmail.com.
authors.forename: Sonia D
authors.initials: SD
authors.lastname: Lourembam
authors.forename: Clara E
authors.initials: CE
authors.lastname: Sawian
authors.forename: Shashi
authors.initials: S
authors.lastname: Baruah
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D008297:Male; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Assam; Complicated malaria; Cytokine; Plasmodium falciparum