Plasma Levels of Tumour Necrosis Factor-Alpha, Interleukin-10, Interleukin-12, Macrophage Inhibition Factor and Transforming Growth Factor-Beta in Children with Severe and Uncomplicated Falciparum Malaria

Eric A Achidi, Tobias O Api

Abstract

The outcome of an infection appears to hinge on a delicate balance between appropriate and inappropriate induction of inflammatory/anti-inflammatory cytokines. However, the role of these mediators in the pathogenesis of severe malaria remains controversial. In this study, plasma levels and ratios of the pro- (TNF-α, IL-12 and MIF), and the anti-inflammatory (IL-10 and TGF-β) cytokines were determined and compared in patients with cerebral malaria (CM), severe malaria anaemia (SMA), uncomplicated malaria (UM), and healthy control (HC) children below 14 years of age. TNF-α, IL-10 and TGF-β levels were significantly different among the four clinical groups, while IL-12 and MIF levels were similar among the clinical groups. TNF-α level were higher in SMA and UM, when compared with HC. Additionally, TNF-α levels were higher (P=0.002) in the combined severe malaria group (CM+SMA, 46.31 ± 44.43), compared to the combined control (UM+HC) group (25.59 ± 26.64). The HC group had lower and higher levels of anti-inflammatory cytokines, IL-10 and TGF-β respectively, when compared to each of the three patient categories. The levels of both IL-10 and TGF-β were significantly higher in UM compared to SMA. A comparison between the ratios of pro- to anti- inflammatory cytokines revealed a significantly higher TNF-α/IL-10 ratio in the HC group, compared to each the patient categories. Malaria parasite density also correlated positively with the levels of TNF-α and IL-10, but negatively with TGF-β level. TNF-α levels also correlated positively with IL-10 and MIF, but negatively with TGF-β levels. Furthermore, a significant negative correlation was observed between IL-10 and TGF-β levels. In conclusion, this study confirms a pathogenic role for TNF-α, with higher ratios of TNF-α to IL-10, and TGF-β associated with severe malaria anaemia in children residing in an endemic area.

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