Plasmodium chabaudi: estradiol suppresses acquiring, but not once-acquired immunity

This study investigates the effect of estradiol (E) on self-healing of Plasmodium chabaudi malaria in mice of the inbred strain C57BL/10. Our data show: (1) Female mice and male castrates are capable of self-healing infections when challenged with 10(6) P. chabaudi-infected erythrocytes. Self-healing is completely suppressed after pretreatment of mice with 12 micrograms E injected sc twice a week for 3 weeks. (2) The suppressive effect of E is prevented by the estrogen receptor blockers tamoxifen and clomiphene. (3) The nonsteroidal E-agonist diethylstilbestrol (DES) also suppresses self-healing. This suppressive DES effect is prevented by tamoxifen. (4) In mice immune to P. chabaudi, neither survival rate nor the course of parasitemia is affected by E, even at 10-fold higher E doses. Our data suggest that the immunosuppressive action of E is a specific genomic effect, i.e., E-induced gene products prevent the development of protective immunity against P. chabaudi.