title: 5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune encephalomyelitis in mice.
abstract: Androstenediol (androst-5-ene-3β,17β-diol; 5-AED), a natural adrenal steroid, has been shown to suppress experimental autoimmune encephalomyelitis (EAE) in female SJL/J mice. We here report that 5-AED limits inflammation and proinflammatory cytokines including TNFα in murine models of carrageenan-induced pleurisy and lippopolysaccaride- (LPS) induced septic shock. 5-AED binds to and transactivates sex steroid receptors with the same general rank order of potency (ERβ > ERα ≫ AR). 5-AED provides benefit in EAE in a dose-dependent fashion, even when treatment is delayed until onset of disease. The minimally effective dose may be as low as 4 mg/kg in mice. However, benefit was not observed when 5-AED was given in soluble formulation, leading to a short half-life and rapid clearance. These observations suggest that treatment with 5-AED limits the production of pro-inflammatory cytokines in these animal models and, ultimately, when formulated and administered properly, may be beneficial for patients with multiple sclerosis and other Th1-driven autoimmune diseases.
authors.affiliation: Department of Biomedical Sciences, School of Medicine, University of Catania, Via Androne 83, 95124 Catania, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.forename: Dominick L
authors.initials: DL
authors.lastname: Auci
authors.forename: Katia
authors.initials: K
authors.lastname: Mangano
authors.forename: Jaime
authors.initials: J
authors.lastname: Flores-Riveros
authors.forename: Sonia
authors.initials: S
authors.lastname: Villegas
authors.forename: James M
authors.initials: JM
authors.lastname: Frincke
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Reading
authors.forename: Halina
authors.initials: H
authors.lastname: Offner