16-Epiestriol, a Novel Anti-Inflammatory Nonglycogenic Steroid, Does Not Inhibit IFN-γ Production by Murine Splenocytes

Abstract

All the steroidal anti-inflammatory drugs currently available are glucocorticoids. The desired anti-inflammatory activities of glucocorticoids frequently are accompanied by adverse side effects, notably glycogenic activities and profound immunosuppression, that can limit clinical use. We recently identified 16-epiestriol, a naturally occurring steroid, as exhibiting significant anti-inflammatory activity without glycogenic activity. In the present study, we compared the effects of 16-epiestriol and hydrocortisone on the capacity of murine splenocytes to produce interferon-y (IFN-y). We injected young adult male BDF1 mice once with 20 mg/kg hydrocortisone or 20, 5, or 1 mg/kg 16-epiestriol and 4 h later harvested the splenocytes. Flow 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 concanavalin A-stimulated IFN-gamma production by spleen cells, as determined by ELISA. Incubating spleen cells from untreated mice in concentrations of 16-epiestriol ranging from 1 mg/ml to 100 pg/ml did not alter profiles of IFN-gamma production, in contrast to the suppressive dose-response effects of hydrocortisone. Collectively, these results support the contention that 16-epiestriol may be a clinically useful safe anti-inflammatory steroid without profound immunosuppressive activities.

Aberrant Synthesis, Metabolism, and Plasma Accumulation of Circulating Estrogens and Estrogen Metabolites in Preeclampsia Implications for Vascular Dysfunction

“…16-epi-estriol has been demonstrated to possess strong anti-inflammatory effects without profound immunosuppressive or glycogenic activities. 31, 32 17-epi-estriol possesses negative effects on inflammatory and adhesion by suppressing TNFα-induced and nitric oxide-mediated VCAM-1 expression. 33 Thus, since preeclampsia is associated with abnormal increased expression of adhesion molecules and increased levels of pro-inflammatory cytokines that induce alterations in vascular vasodilatory responsiveness, 34 our findings suggest the first possibility that low 16-epi-estriol and 17-epi-estriol may potentially contribute to perturbations in inflammatory and impaired adhesion responses in preeclampsia.…”