Dysregulation of cytokines expression in complicated falciparum malaria with increased TGF-β and IFN-γ and decreased IL-2 and IL-12

Cytokine. 2013 Nov;64(2):503-8. doi: 10.1016/j.cyto.2013.08.007. Epub 2013 Sep 4.


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).

Conclusion: 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.

Keywords: Assam; Complicated malaria; Cytokine; Plasmodium falciparum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation
  • Humans
  • Infant
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism*
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism*
  • Malaria, Falciparum / complications*
  • Malaria, Falciparum / genetics
  • Malaria, Falciparum / metabolism
  • Male
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Young Adult


  • Interleukin-2
  • Transforming Growth Factor beta
  • Interleukin-12
  • Interferon-gamma