Plasma interleukin-10:Tumor necrosis factor (TNF)-alpha ratio is associated with TNF promoter variants and predicts malarial complications.

ABSTRACT

In individuals with severe malarial anemia, plasma levels of tumor necrosis factor (TNF)-alpha tend to exceed those of interleukin (IL)-10. In this study, IL-10TNF plasma level ratios <1 were found to be a risk factor for both cerebral malaria and severe anemia (P=.009), whereas higher IL-10TNF ratios were observed more frequently in hyperparasitemic individuals. When considering allelic variants of the TNF promoter in children with severe malaria, carriers of the wild type more frequently had an IL-10TNF ratio >1 (P=.008). In contrast, individuals with a mutation at position -238 of the TNF promoter (TNF(-238A) and TNF(-376A/-238A)) consistently had lower IL-10 than TNF plasma levels (IL-10TNF ratio <1; P=.003). Our results show that, in children with severe malaria, TNF promoter variants influence the balance of IL-10TNF in the plasma, which, in turn, affects the outcome in terms of clinical complications.