Reduced Interleukin?12 and Transforming Growth Factor–?1 in Severe Childhood Malaria: Relationship of Cytokine Balance with Disease Severity

Abstract

Interleukin (IL)—12 and transforming growth factor (TGF)—β1 regulate the balance between pro- and anti-inflammatory cytokines in animal models of malaria. Since the cytokine balance may be an important determinant of whether a protective or a pathogenic immune response develops, plasma cytokine ratios were examined in Gabonese children with various degrees of malarial severity. Severe disease was characterized by high-density parasitemia and severe anemia. IL-12 and TGF-β1 were significantly lower, whereas tumor necrosis factor (TNF)—α and IL-10 were significantly higher in children with severe malaria. The ratios of TGF-β1/IL-12 and IL-10/IL-12 were significantly higher in the severe, compared with the mild, malaria group. In contrast, ratios of TGF-β1/TNF-α and IL-10/TNF-α were significantly lower in the severe malaria group. These results suggest that the inflammatory cascade in severe malaria is characterized by suppression of the protective effects of TGF-β1 and IL-12, and that overproduction of TNF-α may promote deleterious effects, such as severe anemia.