Low Levels of RANTES Are Associated with Mortality in Children with Cerebral Malaria

BACKGROUND: In children with cerebral malaria (CM), serum chemokine levels and associated morbidity and mortality have not been characterized. METHODS: Serum levels of the cytokines interleukin (IL)-1 beta , IL-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor-alpha and the chemokines macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and regulated upon activation, normal T cell expressed and secreted (RANTES) were measured in Ugandan children with CM, in children with uncomplicated malaria (UM), and in healthy children from the community, as control subjects (CCs). RESULTS: Children with CM had lower levels of RANTES and higher levels of all other cytokines and chemokines than CCs (all P<.0001), and they had lower levels of RANTES (P=.004) and higher levels of IL-10 (P=.003), IFN-gamma (P=.007), and IL-1 beta (P=.05) than children with UM. Children with CM who died had lower levels of RANTES (P=.006) and higher of levels of IL-6 (P=.006), IL-10 (P=.01), IFN-gamma (P=.03), and MIP-1 beta (P=.008) than children who survived. After adjustment for other cytokine and chemokine levels, only low levels of RANTES were independently associated with mortality (P=.016). Levels of RANTES correlated with platelet count but were associated with mortality independently of platelet count. CONCLUSIONS: The serum cytokine and chemokine profile of children who die of CM is similar to that of individuals who die of sepsis. Levels of RANTES are significantly lower in children with CM, and very low levels of RANTES are associated with mortality, independently of other cytokine and chemokine levels.