Elevated serum levels of IL-1ra in children with Plasmodium falciparum malaria are associated with increased severity of disease

Animal models suggest that cytokines and chemokines play a role in cerebral malaria (CM) pathogenesis, but levels of a number of cytokines and chemokines thought to be important in the pathogenesis of other infectious diseases are not well characterized in children with CM. Serum levels of granulocyte-colony stimulating factor (G-CSF), interleukin-1 receptor antagonist (IL-1ra), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were measured in 77 children with CM, 70 children with uncomplicated malaria (UM) and 63 healthy community children (CC) in Uganda. Children with CM had elevated serum levels of IL-1ra and IL-8 as compared to children with UM (median levels in pg/ml, 11,891 vs. 6510, P = 0.05, and 63 vs. 41, P = 0.01, respectively). Children with CM who died (n = 4) had higher serum levels than survivors of IL-1ra (median levels in pg/ml, 65,757 vs. 10,355, P = 0.02), G-CSF (709 vs. 117, P = 0.02), and MCP-1 (1275 vs. 216, P = 0.03) but not IL-8 (76 vs. 62, P = NS). Elevated IL-1ra levels are associated with increased disease severity in children with malaria, and very elevated levels of IL-1ra, G-CSF and MCP-1 are seen in children who die of CM.