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 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.
Miller
E
E
The Don and Sybil Harrington Cancer Center, Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, School of Pharmacy, Amarillo 79106, USA.
Bates
R
R
Bjorndahl
J
J
Allen
D
D
Burgio
D
D
Bouma
C
C
Stoll
J
J
Latman
N
N
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004964:Estriol / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D007371:Interferon-gamma; D004964:Estriol; D006854:Hydrocortisone