Testosterone-induced compared with oestradiol-induced immunosuppression against Plasmodium chabaudi malaria.
Testosterone suppresses immunity against malaria caused by Plasmodium chabaudi in B10 mice. Since this effect is probably not mediated through the classical androgen-receptor response, we investigated whether testosterone might act, after aromatization to oestradiol (OE2), through the oestrogen receptor (ER). Indeed, OE2 was found to act immunosuppressively when used at only about 1% of the immunosuppressive dose of testosterone. This becomes evident as an OE2-induced suppression of self-healing of P. chabaudi infections in female and castrated male B10 mice. The immunosuppressive OE2 effect is associated with a 16-fold increase in the circulating level of OE2 and can be prevented by ER blockers such as tamoxifen and clomifene. In contrast, the immunosuppressive effect of testosterone, which is not associated with any changes in the level of OE2, cannot be abolished by ER blockers or by aromatase inhibitors, such as atamestane and drofazar hydrochloride. Moreover, OE2 and testosterone act differently on spleen cells; OE2 induces a decrease in CD(4+)-T-cells, whereas testosterone causes an increase in CD(8+)-T-cells and a decrease in total nucleated spleen cells. The immunosuppressive effect of testosterone, but not that of OE2, can be adoptively transferred to syngeneic mice by nucleated spleen cells, predominantly T-cells. Our data show that the immunosuppressive activity of testosterone, in contrast to OE2, is not mediated through the ER. The immunosuppressive action of testosterone is therefore thought to be primarily mediated through a non-genomic mechanism.
Benten
W P
WP
Division of Parasitology, Heinrich Heine University, Düsseldorf, Germany.
Wunderlich
F
F
Herrmann
R
R
Kühn-Velten
W N
WN
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002996:Clomiphene / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D007165:Immunosuppression Therapy; D008288:Malaria / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009919:Orchiectomy; D016788:Plasmodium chabaudi; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology; D013629:Tamoxifen / Q000494:pharmacology; D013739:Testosterone / Q000494:pharmacology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D013629:Tamoxifen; D002996:Clomiphene; D013739:Testosterone; D004958:Estradiol