falciparum-infected groups. Plasma concentrations of CXCL16 in NEG patients were 2930 pg/ml (mean) and the levels were enhanced in those with P. falciparum, to 5160 pg/ml in MM and 8840 pg/ml in SM cases. CXCL9 and CXCL16 levels were clearly higher (P < 0·0001) in SM than in NEG, and CXCL9 levels in SM were higher than those of MM patients (P < 0·0001). At 48–60 h post-anti-malarial treatment (Fig. 3), significantly diminished cytokine concentrations were detected for IL-10, IL-13 and the

chemokines MIG/CXCL9, CXCL16 and MIP-3α/CCL20 (not shown). The mean levels of IL-17F, Romidepsin purchase IL-27, IL-31 and IL-33 did not change at 48–60 h post-anti-malaria treatment and with reduced parasitaemia. In P. falciparum-infected infants, the levels of MIP3-α/CCL20 (r2 = 0·28; P = 0·0002) and MIG/CXCL9 (r2 = 0·33, P = 0·0005) were correlated positively with parasite density, while IL-27 displayed a weak negative correlation (r2 = −0·17; P = 0·01). Naturally acquired protective immunity against malaria requires subclass-specific antibody responses [16–18], and the secretion of cytokines, chemokines and further immune mediators is essential for the regulation both of cellular effector mechanisms against P. falciparum blood-stage parasites and of organ-specific inflammation and pathogenesis [19,20]. In MM and SM infants substantial cytokine Selleckchem GS-1101 and chemokine levels were detected, which disclosed

both innate and memory immune responsiveness. The first parasite encounter and sensitization to P. falciparum antigens may already occur prenatally and continue in infants shortly after birth [21]. P. falciparum infection during pregnancy is a major health problem in our study area [22,23], and prenatal and early life contact with plasmodial antigens has to be considered as a regularity. In infants, antibody responses and pronounced parasite-specific IL-10 production were found to be associated with faster P. falciparum parasite clearance [24], and the higher longevity of regulatory T cell

(Treg)-type IL-10 compared to Th1-type IFN-γ responses [25] suggested that prenatal and early postnatal sensitization with P. falciparum antigens has occurred [26,27]. It is noteworthy that parasite-specific Tyrosine-protein kinase BLK IL-10 responses were observed frequently and of high magnitude in umbilical cord blood cells from newborns of infected mothers [21–23,28]. In the present work, plasma IL-10 levels were not correlated with parasite densities or the infants’ age, and this further supported early life P. falciparum-specific immune sensitization and IL-10 induction. The role of IL-10 in malaria pathogenesis is controversial. High IL-10 levels were associated with cerebral malaria [13], with high parasite density and severe disease in children [29,30], while lower plasma concentrations of IL-10 occurred in those with severe malarial anaemia [13,30].