Reduced interleukin-12 and transforming growth factor-ss 1 in severe childhood malaria: Relationship of cytokine balance with disease severity

Interleukin (IL)-12 and transforming growth factor (TGF)-beta 1 regulate th e balance between pro- and anti-inflammatory cytokines in animal models of malaria. Since the cytokine balance may be an important determinant of whet her 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-beta 1 were significantly lower, whereas tumor necrosis factor (TNF)-alpha and IL-10 were significantly higher in childre n with severe malaria. The ratios of TGF-beta 1/IL-12 and IL-10/IL-12 were significantly higher in the severe, compared with the mild, malaria group. In contrast, ratios of TGF-beta 1/TNF-alpha and IL-10/TNF-alpha were signif icantly lower in the severe malaria group. These results suggest that the i nflammatory cascade in severe malaria is characterized by suppression of th e protective effects of TGF-beta 1 and IL-12, and that overproduction of TN F-alpha may promote deleterious effects, such as severe anemia.