Interleukin-10 Inhibits Tumor Necrosis Factor Production but Not Antigen-Specific Lymphoproliferation in Acute Plasmodium falciparum Malaria

In vivo interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-γ production was measured at the mRNA transcript and protein levels in patients acutely infected with Plasmodium falciparum and during convalescence. Both IL-10 and IFN-γ but not IL-2 were produced regardless of the patients' clinical severity. IL-4 production was variable, Circulating IFN-γ and IL-10 were significantly higher in patients with severe disease (P < .01 and .001, respectively). In vitro stimulation of peripheral blood mononuclear cells (PBMC) by malarial antigens during acute infection showed that although there was no lymphoproliferation, the cells could produce IL-10 and IFN-γ. Recombinant human IL-10 completely abolished in vitro tumor necrosis factor (TNF)-α production in response to malarial antigens, as well as the antigen-specific proliferative response of convalescent patients. However, anti-IL-10 was insufficient to restore proliferation of PBMC from acutely infected patients. These findings suggest that IL-10 may have an important negative feedback action on the production of inflammatory cytokines in acute falciparum malaria without contributing to the defect in antigen-specific proliferation.