title: Dietary testosterone suppresses protective responsiveness to Plasmodium chabaudi malaria.
abstract: 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.
authors.affiliation: Max-Planck-Institute of Immunobiology, Freiburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Mossmann
authors.forename: W P
authors.initials: WP
authors.lastname: Benten
authors.forename: C
authors.initials: C
authors.lastname: Galanos
authors.forename: M
authors.initials: M
authors.lastname: Freudenberg
authors.forename: W N
authors.initials: WN
authors.lastname: Kühn-Velten
authors.forename: H
authors.initials: H
authors.lastname: Reinauer
authors.forename: F
authors.initials: F
authors.lastname: Wunderlich
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D016207:Cytokines / Q000097:blood; D004032:Diet; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D008107:Liver Diseases / Q000276:immunology; D008288:Malaria / Q000276:immunology*; D008777:Methyltestosterone / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000166:cytology; D016788:Plasmodium chabaudi; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013739:Testosterone / Q000097:blood*; D045165:Testosterone Congeners / Q000633:toxicity*
chemical_list: D016207:Cytokines; D045165:Testosterone Congeners; D013739:Testosterone; D008777:Methyltestosterone