TY - JOUR
T1 - 5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune encephalomyelitis in mice
AU - Nicoletti, Ferdinando
AU - Auci, Dominick L.
AU - Mangano, Katia
AU - Flores-Riveros, Jaime
AU - Villegas, Sonia
AU - Frincke, James M.
AU - Reading, Christopher L.
AU - Offner, Halina
PY - 2010
Y1 - 2010
N2 - 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 (ERβERα≫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 4mg/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.
AB - 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 (ERβERα≫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 4mg/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.
UR - http://www.scopus.com/inward/record.url?scp=79955658198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955658198&partnerID=8YFLogxK
U2 - 10.4061/2010/757432
DO - 10.4061/2010/757432
M3 - Article
C2 - 21188238
AN - SCOPUS:79955658198
SN - 2090-0422
VL - 1
JO - Autoimmune Diseases
JF - Autoimmune Diseases
IS - 1
M1 - 757432
ER -