Malaria infection is associated with the release of proinflammatory cytokines including TNF-alpha, IFN-gamma, IL-1, and IL-6. These cytokines play important roles in mediating the disease severity and involved in the pathogenesis and immunopathological reactions during the infection.
IL-18 is a potent pro-inflammatory cytokine and inducer of other cytokines release. In this study, we investigated the effect of modulating IL-18 production on the release of pro-inflammatory and anti-inflammatory cytokines (TNF-alpha, IFN-gamma, IL-1, IL-6 and IL-10) during malaria infection.
Plasmodium berghei infection in ICR mice was used as model for malaria infection. Mice were inoculated with parasitized red blood cells from donor mouse infected with P. berghei. Control animals received normal uninfected red blood cells. IL-18 production during the infection was modulated by treatment with the rIL-18, rIL-18 binding protein and anti-IL-18 monoclonal antibody. Blood samples for plasma were collected from the animals on day 1, 3 and 5 following inoculation and treatment. ELISA method was employed to measure the levels of cytokines in the plasma.
IL-18 level in the plasma of malarial mice were found to be significantly elevated and positively correlated with the percentage degree of parasitaemia. Inhibition and neutralization of IL-18 production caused significant decrease in the plasma levels of pro-inflammatory cytokines TNF-alpha, IFN-gamma, IL-1 and IL-6. In contrast, the anti-inflammatory cytokine IL-10 was significantly increased. Treatment with rIL-18 on the other hand caused significant increase in pro-inflammatory cytokines plasma levels, whereas the anti-inflammatory cytokine level was significantly reduced.
Results proved the involvement of IL-18 in malaria infection. Its positive modulatory effects on the release of pro-inflammatory and anti-inflammatory cytokines during the infection may suggest its crucial role(s) in the pathogenesis of the infection. Results also suggest the IL-18 potential as an immunotherapeutic target in malaria therapy.
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