Enhancement of in vivo humoral immunity by estrogen: permissive effect of a thymic factor.

Physiological levels of estrogen enhance humoral immune responses. Several in vitro studies indicate the hormone to have a direct effect on immune cells, and other studies show that estrogen may affect humoral immunity indirectly through the thymus. Therefore, we have conducted experiments to investigate the requirement of the thymus in the enhancement of humoral immune responsiveness by estrogen. In Exp I, adult ovariectomized Lewis rats were thymectomized or sham thymectomized and given estradiol (E2; 0.25 microgram E2 in sesame oil, sc, once every 4 days) or the oil vehicle in a 2 x 2 factorial design, and their antifluorescein responses were followed by enzyme-linked immunosorbant assay across 21 days. Only animals that were thymus intact and given estrogen replacement showed significantly (P less than 0.05) greater serum antifluorescein titers than all other treatments. In Exp II, ovariectomized thymectomized rats were submitted to a 2 x 3 factorial design of oil vehicle or E2 replacement and saline, gelatin, or thymus replacement (thymosin fraction 5; 1 mg/kg in saline, sc). As described above, only the animals receiving both thymosin fraction 5 and E2 replacement displayed antifluorescein titers that were significantly (P less than 0.03) increased over titers of all other treatment groups. These results indicate that the enhancement of in vivo humoral immunity by estrogen requires the thymus, and that a constitutive thymic factor, found in thymosin fraction 5, exerts a permissive influence on the action of E2 outside the thymus to increase a specific humoral immune response.