Plasma Concentration of Malaria Parasite-Derived Macrophage Migration Inhibitory Factor in Uncomplicated Malaria Patients Correlates with Parasitemia and Disease Severity

Host macrophage migration inhibitory factor (MIF) has been implicated in the pathogenesis of malaria infections. Several Plasmodium parasite-derived MIFs were identified to have the potential to regulate host immune response. However, the role of Plasmodium MIFs in the immunopathogenesis of malaria infection and the relationships between these mediators and inflammatory cytokines remained unclear. In this study, we have investigated two Plasmodium MIFs in peripheral blood of uncomplicated malaria patients and analyzed their correlations with several major factors during malaria infection. We found that both Plasmodium falciparum MIF (PfMIF) and Plasmodium vivax MIF (PvMIF) levels in patients were positively correlated with parasitemia, tumor necrosis factor alpha, interleukin-10 (IL-10), and monocyte chemoattractant protein 1 but were not correlated with transforming growth factor beta 1 and IL-12. Of interest was that the PvMIF level was positively correlated with host body temperature and human MIF (HuMIF) concentrations. Moreover, multiple stepwise regression analysis also showed that parasitemia, IL-10, and HuMIF expression were significant predictors of Plasmodium MIF production. In addition, during antimalarial drug treatment, the decreasing of Plasmodium MIF concentrations was followed by parasitemia in most patients. Our results suggested that the Plasmodium MIF circulating level reflects the level of parasitemia and thus was closely correlated with disease severity in uncomplicated malaria. Therefore, this factor has the potential to be a promising disease predictor and is applicable in clinical diagnosis.