Anti-inflammatory mechanisms of 5 [alpha]-reduced glucocorticoids: potential dissociated steroids

摘要: We recently showed that 5α-reduced metabolites of corticosterone (B), namely 5α-dihydrocorticosterone (5αDHB) and 5α-tetrahydrocorticosterone (5αTHB), possess similar anti-inflammatory properties to B, but have lesser metabolic effects. Here, we explored the anti-inflammatory mechanisms of these 5α-reduced metabolites in vitro. Data are mean% suppression/induction, compared by one way ANOVA,* P< 0.05 versus vehicle.In RAW264. 7 murine macrophages stimulated with lipopolysaccharide (LPS, 30 ng/ml, 24 h), TNFα and IL6 release was suppressed by B (1 μM; 61.7%*, 92.2%*, respectively), 5αDHB (1 μM; 20.4%*, 68.8%*) and 5αTHB (1 μM; 40.3%*, 47.5%* respectively), effects that were inhibited by co-incubation with the glucocorticoid receptor (GR) antagonist RU486 (1 μM). Relevance to normal cells was confirmed in LPS-stimulated (100 ng/ml, 24 h) bone-marrow-derived murine macrophages, in …