Differential interleukin-10 expression in interferon regulatory factor-1 deficient mice during Plasmodium berghei blood-stage infection

Mice deficient of functional interferon regulatory factor-1 (IRF-1-/-) by t argeted gene disruption infected with a lethal murine malaria strain. Plasm odium berghei ANKA survived longer than its wild-type littermates despite t he inability to induce appreciable amounts of interferon-gamma (IFN-gamma) and nitric oxide. In addition, infected IRF-1-/- mice displayed less organ injury with reduced necrosis and inflammation. Both wild-type and IRF-1-/- mice treated with exogenous interleukin-12 (IL-12) suffered extensive organ damage with corresponding up regulation of IFN-gamma, suggesting the patho genic potential of IL-12 and IFN-gamma. IL-10 is a cytokine produced by CD4 (+) T lymphocytes belonging to the Th2 subset. Expression of IL-10 in the w ildtype mice col related with the severity of the infection, with higher mR NA expression towards the later stage of infection. In cont, ast to the wil d-type mice, IL-10 levels in the IRF-1-/- mice were induced early in the in fection and decreased gradually as the infection progressed. Both untreated and IL-12 treated wild-type mice appeared to follow a Th1-like immune resp onse early in the infection and a Th2-like immune response Intel in the inf ection. However, the IRF-1-/- mice were able to launch an altered immune re sponse with a Th2-like immune response early in the infection. These findin gs suggest that IL-10 expression in the IRF-1-/- mice during the early stag e of P. berghei ANKA infection could play an important role in suppressing pathogenic effects of a cell mediated immune response and promoting protect ive immunity against the parasite.