Reduced interleukin-12 and transforming growth factor-beta1 in severe childhood malaria: relationship of cytokine balance with disease severity.
Interleukin (IL)-12 and transforming growth factor (TGF)-beta1 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-beta1 were significantly lower, whereas tumor necrosis factor (TNF)-alpha and IL-10 were significantly higher in children with severe malaria. The ratios of TGF-beta1/IL-12 and IL-10/IL-12 were significantly higher in the severe, compared with the mild, malaria group. In contrast, ratios of TGF-beta1/TNF-alpha and IL-10/TNF-alpha 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-beta1 and IL-12, and that overproduction of TNF-alpha may promote deleterious effects, such as severe anemia.
Perkins
D J
DJ
Centers for Disease Control and Prevention, Division of Parasitic Diseases, Molecular Vaccine Section, Atlanta, GA 30341, USA. dqp5@cdc.gov
Weinberg
J B
JB
Kremsner
P G
PG
D002648:Child; D002675:Child, Preschool; D005681:Gabon; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000096:biosynthesis*; D016778:Malaria, Falciparum / Q000378:metabolism*; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12