5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune encephalomyelitis in mice

Ferdinando Nicoletti, Dominick L. Auci, Katia Mangano, Jaime Flores-Riveros, Sonia Villegas, James M. Frincke, Christopher L. Reading, Halina Offner

Research output: Contribution to journalArticle

15 Scopus citations

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 (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.

Original languageEnglish (US)
Article number757432
JournalAutoimmune Diseases
Volume1
Issue number1
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Immunology and Microbiology (miscellaneous)

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    Nicoletti, F., Auci, D. L., Mangano, K., Flores-Riveros, J., Villegas, S., Frincke, J. M., Reading, C. L., & Offner, H. (2010). 5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune encephalomyelitis in mice. Autoimmune Diseases, 1(1), [757432]. https://doi.org/10.4061/2010/757432