Our previous observation that B-cell-deficient JH-/- mice utilize T cell-dependent immunity to suppress acute Plasmodium chabaudi adami-induced
malaria but then develop chronic low-level
parasitemia prompted this study of control mechanisms for chronic
parasitemia. When we infected JH-/- mice with blood-stage parasites, chronic
parasitemia exacerbated after the 6th month and persisted for up to 17 months. This exacerbation of
parasitemia could not be attributed to host aging because the time-course of acute
infection in naïve aged mice was nearly identical to that seen in young mice. Nor could exacerbated
parasitemia be attributed to mutation in the parasite genome resulting in increased virulence; when subinoculated into naïve JH-/- mice, parasites from chronically infected JH-/- mice with exacerbated
parasitemia produced acute stage
parasitemia profiles in most recipients comparable to those seen in JH-/- mice upon
infection with the original stabilate material. Of the pro-inflammatory
cytokines measured, including IFNgamma,
TNFalpha, IL-12p70, and MCP-1beta, none were significantly different in the sera of mice with exacerbated
parasitemia compared to uninfected controls. Levels of
IL-6 were significantly (P=0.002) less in the sera of mice with exacerbated
parasitemia. Serum levels of the anti-inflammatory
cytokine,
TGFbeta, were significantly depressed in chronically infected JH-/- mice compared to uninfected controls. In contrast,
IL-10 levels were markedly increased. These findings suggest that the
cytokine balance may be disturbed during
chronic malaria, thereby impacting on mechanisms that modulate levels of
parasitemia.