Involvement of interleukin-18 in severe Plasmodium falciparum malaria

Serum levels of interleukin-18 (IL-18), interferon-gamma (IFN-gamma), and immunoglobulin E (IgE) were determined for 96 patients with Plasmodium falciparum malaria admitted to hospital, Bangkok, Thailand in the period 1998-2000. The patients were divided into 3 groups, i.e. uncomplicated, severe and cerebral malaria according to WHO criteria (2000). Elevation of IL-18 levels was observed in all 3 groups, with a tendency for higher levels in cases with severe malaria throughout the course of the disease. Moreover, there was a significant correlation between IL-18 levels and the extent of parasitaemia among patients with severe malaria. However, IL-18 levels decreased more significantly in patients with cerebral malaria compared with the other groups in the late stage of the disease. Elevated levels of IFN-gamma were also observed in all groups of patients, especially in those with severe or cerebral malaria, and the levels in patients with cerebral malaria remained significantly higher than in those with uncomplicated malaria during days 4-7 post-treatment, suggesting the involvement of IFN-gamma in disease severity. Meanwhile, no significant difference was observed in IgE levels between the severe and uncomplicated groups of patients with helminth infection, although IgE levels were significantly higher in helminth-infected patients than uninfected patients. These results suggest that IL-18 plays a key role in inducing severe malaria through another pathway, such as elevation of IFN-gamma, rather than its IgE inducing activity.