Dietary testosterone suppresses protective responsiveness to Plasmodium chabaudi malaria

This study investigates the effect of orally administered testosterone on serum testosterone levels and immune responses including outcome of Plasmodium chabaudi malaria. Female C57BL/10 mice were fed on a diet impregnated with 17 alpha-methyl-testosterone for 3 weeks. This raised the circulating testosterone levels from 0.28 ng/ml to 2.69 ng/ml on the average. In these mice, blood-stage infections of P. chabaudi resulted in a lethal outcome, whereas protective immunity developed in about 80% of mice fed on control diet without testosterone. Dietary 17 alpha-methyl-testosterone reduced the capacity of peritoneal cells to generate reactive oxygen intermediates after stimulation with C3b-coated zymosan and phorbol-myristate-acetate. Also, mice fed on dietary 17 alpha-methyl-testosterone responded to heat-killed Salmonella typhimurium with a higher increase in serum TNF, whereas the induced increase in the production of IL-10 by spleen cells was largely suppressed and no effect was found with respect to the production of IFN-gamma and IL-4. Our data indicate that the method of oral administration of 17 alpha-methyl-testosterone raises circulating testosterone to levels that impair protective immune responses to P. chabaudi malaria.