Genetic evidence for the aggravation of plasmodium falciparum malaria by interleukin 4

Abstract

Background: Severe malaria (SM) due to Plasmodium falciparum causes millions of child deaths in sub-Saharan Africa. It comprises a variety of clinical disorders, including cerebral malaria (CM) and severe anemia (SA). In previous work, we have shown that interferon γ and interleukin 12 protect against CM. Here, we investigated whether interleukin 4 (IL-4) aggravates the risk of severe disease. Methods: We prospectively recruited children with CM (np240), SA (np101), and uncomplicated malaria (UM) (np42) in Bamako, Mali, and measured IL-4 production in plasma by enzyme-linked immunosorbent assay. We then assessed the influence of 11 polymorphisms on predisposition to SM by the family-based association test (FBAT). Results: IL-4 concentrations were higher in children with CM than in children with UM during malaria (Pp.003). FBAT analyses showed that the most significant association was between the IL4 variable-number tandem repeat (VNTR) 1/2 genotype and SM (P