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 Citations (Scopus)

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

Fingerprint

Androstenediol
Pleurisy
Autoimmune Experimental Encephalomyelitis
Septic Shock
Cytokines
Steroid Receptors
Carrageenan
Autoimmune Diseases
Multiple Sclerosis
Half-Life
Animal Models
Steroids
Inflammation
Therapeutics

ASJC Scopus subject areas

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

Cite this

Nicoletti, F., Auci, D. L., Mangano, K., Flores-Riveros, J., Villegas, S., Frincke, J. M., ... 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

5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune encephalomyelitis in mice. / Nicoletti, Ferdinando; Auci, Dominick L.; Mangano, Katia; Flores-Riveros, Jaime; Villegas, Sonia; Frincke, James M.; Reading, Christopher L.; Offner, Halina.

In: Autoimmune Diseases, Vol. 1, No. 1, 757432, 2010.

Research output: Contribution to journalArticle

Nicoletti, F, Auci, DL, Mangano, K, Flores-Riveros, J, Villegas, S, Frincke, JM, Reading, CL & Offner, H 2010, '5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune encephalomyelitis in mice', Autoimmune Diseases, vol. 1, no. 1, 757432. https://doi.org/10.4061/2010/757432
Nicoletti, Ferdinando ; Auci, Dominick L. ; Mangano, Katia ; Flores-Riveros, Jaime ; Villegas, Sonia ; Frincke, James M. ; Reading, Christopher L. ; Offner, Halina. / 5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune encephalomyelitis in mice. In: Autoimmune Diseases. 2010 ; Vol. 1, No. 1.
@article{cddc6188998b40b4b50e4dfc7b20b6ef,
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 (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.",
author = "Ferdinando Nicoletti and Auci, {Dominick L.} and Katia Mangano and Jaime Flores-Riveros and Sonia Villegas and Frincke, {James M.} and Reading, {Christopher L.} and Halina Offner",
year = "2010",
doi = "10.4061/2010/757432",
language = "English (US)",
volume = "1",
journal = "Autoimmune Diseases",
issn = "2090-0422",
publisher = "Hindawi Publishing Corporation",
number = "1",

}

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

VL - 1

JO - Autoimmune Diseases

JF - Autoimmune Diseases

SN - 2090-0422

IS - 1

M1 - 757432

ER -