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

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