berghei-infected mice [43], and in Ghanaian children cerebral malaria mortality was not associated with IL-17 [15]. While IL-17F levels were similar in NEG, MM and SM infants, the cytokine IL-31, which has comparable effects to IL-17 [44], was highest in SM patients. IL-17 and IL-31 both have

additive effects on secretion of cytokines and chemokines [44,45], and ubiquitin-Proteasome system IL-31, a member of the gp130/IL-6 cytokine family [45], may recruit polymorphonuclear cells, monocytes and T cells to an inflammatory site in vivo[46]. IL-31 will induce the genes of inflammatory chemokines MIP-1β, MIP-3α, MIP-3β[47,48] and proinflammatory cytokines IL-6, IL-8, IL-16 and IL-32 [44,45]. IL-31-receptor-deficiency in mice injected with Schistosoma mansoni eggs resulted in severe

Akt inhibitor pulmonary inflammation, enlarged granuloma and significantly more IL-4, IL-5 and IL-13 than in wild-type mice [48]. In allergic asthma patients, serum levels of IL-31 were elevated above controls [49], a further suggestion that the IL-31/IL-31R signalling pathway will regulate type 2 inflammations [48]. Another key player promoting Th2 type responses, the cytokine IL-33, is considered a mediator of pathology with allergies and septic shock [50–52]; IL-33 was suggested to function as an alarmin [53], to alert after endothelial or epithelial cell damage during trauma, stress or infection [53]. IL-33 levels were enhanced in infants with MM and SM, clearly above NEG, Astemizole correlated positively with parasite densities, and diminished strongly following parasite clearance. Sequestration of P. falciparum-infected erythrocytes or the release of merozoites may have amplified IL-33 production by endothelial cells, and additional cytokines augmented by IL-33 are IL-5, IL-13, TNF and IL-3 [54]. Furthermore, IL-33 will promote splenomegaly, blood eosinophilia and epithelial hyperplasia, massive mucus production in lungs

and pulmonary inflammation [55]. To what extent the enhanced production of IL-31 and IL-33 may contribute to pathogenesis of acute P. falciparum infection to cerebral inflammation and vascular obstructions should be investigated further. For the development of cerebral malaria, an important role has been attributed to cytokines and chemokines [56,57]. With severe P. falciparum infection an increased production of MCP-1/CCL2, MIP-1α and MIP-1β, and also IL-8/CXCL8, has been observed [9,13], and the mortality risk with cerebral malaria (CM) was associated independently with the serum concentration of IP-10/CXCL10 [15]. The chemokines IP-10/CXCL10 and MIG/CXCL9, together with their common receptor CXCR3, are required for the development of murine CM [58]. MIG/CXCL9 and its receptor are expressed predominantly in Th1 cells, and MIG/CXCL9 is considered to be a predictive marker for antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) in volunteers immunized with irradiated P. falciparum sporozoites [59].