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

Abstract

BackgroundIn 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. MethodsWe 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. ResultsHigher 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). ConclusionOur 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.