SUMMARYHuman hookworm infections are distributed widely in tropical areas and have a significant impact on host morbidity and human health. In the present study, we investigated the cellular responsiveness and cytokine production in peripheral blood mononuclear cells (PBMC) from Necator americanus-infected schoolchildren who had recently received chemotherapy, and compared them with non-infected endemic controls. Hookworm patients and treated, egg-negative individuals showed a lower cellular reactivity against phytohaemagglutinin (PHA) and hookworm antigen when compared with eggnegative endemic controls. The baseline production of proinflammatory tumour necrosis factor-a (TNFa ) in PBMC from infected patients and treated, egg-negative individuals was elevated. On the other hand, PHA-or hookworm antigen-induced interleukin (IL)-12 and interferon (IFN)-g secretion was higher in endemic controls than in hookworm patients, who either continued egg-positive or were eggnegative after treatment. Also, PBMC from endemic controls secreted more IL-5 and IL-13 than the other patient groups. Opposite to that, the spontaneous as well as the antigen-driven IL-10 secretion was lower in endemic controls when compared with the other groups. In summary, patently hookworminfected as well as egg-negative treated patients disclosed an elevated spontaneous cellular secretion of proinflammatory TNF-a , a prominent secretion of regulatory Th2-type IL-10 and an impaired production of IL-12, IFN-g , IL-5 and IL-13.

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The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and interferon (IFN)-gamma secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-alpha, IL-12 and IFN-gamma was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P < 0.05), whereas parasite-specific IgE antibody levels were similarly high in infected individuals and in endemic controls. In summary, chronically infected Ascaris and Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-alpha, IFN-gamma and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage.

SummaryCytokine 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)-a/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-a/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-a/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-a/ 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.