| Autor: |
Ferdinando Nicoletti, Dominick L. Auci, Katia Mangano, Jaime Flores-Riveros, Sonia Villegas, James M. Frincke, Christopher L. Reading, Halina Offner |
| Jazyk: |
angličtina |
| Rok vydání: |
2010 |
| Předmět: |
|
| Zdroj: |
Autoimmune Diseases, Vol 2010 (2010) |
| Druh dokumentu: |
article |
| ISSN: |
2090-0430 |
| DOI: |
10.4061/2010/757432 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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