PLASMODIUM-CHABAUDI CHABAUDI (AS) - INFLAMMATORY CYTOKINES AND PATHOLOGY IN AN ERYTHROCYTIC-STAGE INFECTION IN MICE

We have sought to characterize Plasmodium chabaudi chabaudi infection in mice for use as a model for malaria pathology. Different mouse stra ins vary in their susceptibility to the erythrocytic stages of this pa rasite and this is manifested not only in the outcome of infection (su rvival versus death) but also by differences in the numbers of circula ting parasites at the peak of infection. We have shown that regardless of final outcome, both resistant and susceptible mice exhibit other p arameters of disease such as loss in body weight and anemia. By contra st, other parameters such as hypothermia appear more severe in suscept ible mice. The severe symptoms coincide with high levels of inflammato ry cytokines in the circulation of susceptible mice: not seen in H-a-m atched resistant mice. However, levels of mRNA for the same cytokines, measured in the spleen of the same mice was not significantly differe nt between the two strains. Neutralization of IFN-gamma in vivo led to an increase in parasitemia, in both susceptible and resistant mice, b ut did not affect the final outcome of disease. Indeed, symptoms were exacerbated in the absence of IFN-gamma, presumably because of larger numbers of circulating parasites. These data suggest that IFN-gamma do es not directly contribute to the lethal outcome of infection in susce ptible strains of mice. (C) 1998 Academic Press.