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

Chandy C. John, Robert Opika‐Opoka, Justus Byarugaba, Richard Idro, Michael J. Boivin
2006 Journal of Infectious Diseases  
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)-1b, IL-6, IL-10, interferon (IFN)-g, and tumor necrosis factor-a and the chemokines macrophage inflammatory protein (MIP)-1a, MIP-1b, and regulated upon activation, normal T cell expressed and secreted (RANTES) were measured in Ugandan children with CM, in children with uncomplicated malaria (UM),
more » ... d 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 ), and they had lower levels of RANTES ( ) and higher levels of IL-10 ( ), P ! .0001 P p .004 P p .003 IFN-g ( ), and IL-1b ( ) than children with UM. Children with CM who died had lower levels of P p .007 P p .05 RANTES ( ) and higher of levels of IL-6 ( ), IL-10 ( ), IFN-g ( ), and MIP-1b P p .006 P p .006 P p .01 P p .03 ( ) than children who survived. After adjustment for other cytokine and chemokine levels, only low levels P p .008 of RANTES were independently associated with mortality ( ). Levels of RANTES correlated with platelet P p .016 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. Cerebral malaria (CM) is one of the deadliest complications of Plasmodium falciparum infection, with mortality rates of 15%-40% [1]. Although the pathogenesis of CM is likely multifactorial, the balance between specific cytokines and chemokines produced in response to infection with P. falciparum is thought to play an important role in CM and other forms of severe malaria. Inflammatory Th1-type cytokines (e.g., tumor necrosis factor [TNF]-a, interferon [IFN]-g, interleukin [IL]-1b, and IL-6) are thought to be critical to the control of exoerythrocytic and erythrocytic P. falcipa-
doi:10.1086/506623 pmid:16941352 fatcat:7qexujzn2feb7kq2i4hclz6fyu