16-epiestriol, a novel anti-inflammatory nonglycogenic steroid, does not inhibit IFN-gamma production by murine splenocytes

All the steroidal anti-inflammatory drugs currently available are glucocort icoids, The desired anti-inflammatory activities of glucocorticoids frequen tly are accompanied by adverse side effects, notably glycogenic activities and profound immunosuppression, that can limit clinical use. We recently id entified 16-epiestriol, a naturally occurring steroid, as exhibiting signif icant anti-inflammatory activity without glycogenic activity. In the presen t study, we compared the effects of 16-epiestriol and hydrocortisone on the capacity of murine splenocytes to produce interferon-gamma (IFN-gamma). We injected young adult male BDF1 mice once with 20 mg/kg hydrocortisone or 2 0, 5, or 1 mg/kg 16-epiestriol and 4 h later harvested the splenocytes, Flo w cytometric analysis confirmed that 16-epiestriol did not alter the number of CD3(+) T cells in the spleen, In contrast to the suppressive effects of hydrocortisone, none of the 16-epiestriol concentrations inhibited concana valin A-stimulated IFN-gamma production by spleen cells, as determined by E LISA. Incubating spleen cells from untreated mice in concentrations of 16-e piestriol ranging from 1 mg/ml to 100 pg/ml did not alter profiles of IFN-g amma production, in contrast to the suppressive dose-response effects of hy drocortisone, Collectively, these results support the contention that 16-ep iestriol may be a clinically useful safe anti-inflammatory steroid without profound immunosuppressive activities.