Proinflammatory and regulatory cytokines and chemokines in infants with uncomplicated and severe<i>Plasmodium falciparum</i>malaria

Cytokine and chemokine levels were studied in infants (<5 years) with uncomplicated (MM) and severe malaria tropica (SM), and in Plasmodium falciparum infection-free controls (NEG). Cytokine plasma levels of interleukin (IL)-10, IL-13, IL-31 and IL-33 were strongly elevated in MM and SM compared to NEG (P<0·0001). Inversely, plasma concentrations of IL-27 were highest in NEG infants, lower in MM cases and lowest in those with SM (P<0·0001, NEG compared to MM and SM). The levels of the chemokines macrophage inflammatory protein (MIP3)-α/C-C ligand 20 (CCL20), monokine induced by gamma interferon (MIG)/CXCL9 and CXCL16 were enhanced in those with MM and SM (P<0·0001 compared to NEG), and MIP3-α/CCL20 and MIG/CXCL9 were correlated positively with parasite density, while that of IL-27 were correlated negatively. The levels of 6Ckine/CCL21 were similar in NEG, MM and SM. At 48-60 h post-anti-malaria treatment, the plasma concentrations of IL-10, IL-13, MIG/CXCL9, CXCL16 and MIP3-α/CCL20 were clearly diminished compared to before treatment, while IL-17F, IL-27, IL-31 and IL-33 remained unchanged. In summary, elevated levels of proinflammatory and regulatory cytokines and chemokines were generated in infants during and after acute malaria tropica. The proinflammatory type cytokines IL-31 and IL-33 were enhanced strongly while regulatory IL-27 was diminished in those with severe malaria. Similarly, MIP3-α/CCL20 and CXCL16, which may promote leucocyte migration into brain parenchyma, displayed increased levels, while CCL21, which mediates immune surveillance in central nervous system tissues, remained unchanged. The observed cytokine and chemokine production profiles and their dynamics may prove useful in evaluating either the progression or the regression of malarial disease.