ESTROGEN INDUCES SUPPRESSION OF NATURAL-KILLER-CELL CYTOTOXICITY AND AUGMENTATION OF POLYCLONAL B-CELL ACTIVATION

Estrogen displays potent immunoregulatory properties. In the present s tudy we investigated the in vivo effect of estrogen on natural killer (NK) cell cytotoxic activity in several mouse strains. After castratio n, 17 beta-estradiol was administered in low or high doses. After 3-6 weeks of hormone administration an in vivo Cr-51-release assay with YA C-1 cells as target cells was performed. In all mouse strains, estradi ol reduced NK cell cytotoxicity in a dose-dependent manner. However, s ome mouse strains displayed a high (> 50%) degree of estrogen-mediated suppression of NK cells (C3H/N, DBA/1, and NZB/W mice), whereas other s displayed low (<30%) susceptibility (C57BL/6 and MRL/pr/lpr mice). W e also quantitated the frequency of Ig-producing spleen cells in mice receiving 17 beta-estradiol subcutaneously and/or antibodies to NK cel ls (anti-asialo GM1) intraperitonealy. Here, administration of estroge n for 31 weeks but not for 4 weeks significantly increased the frequen cy of IBG and IgM-producing cells. Repeated injections of anti-asialo GM1 for 4 weeks raised the frequency of IgG producing cells several-fo ld. We hypothesize that estrogen-mediated suppression of NK cells down regulates the inhibitory signals from these cells on B cells thus resu lting in increased frequency of Ig-producing cells. (C) 1994 Academic Press, Inc.