HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression

• Main Authors: Frincke James M (Author), White Steven K (Author), van Heeckeren Anna M (Author), Mangano Katia (Author), Nicoletti Ferdinando (Author), Pieters Raymond (Author), Wang Angela (Author), Conrad Douglas (Author), Reading Christopher L (Author), Stickney Dwight (Author), Auci Dominick L (Author)
• Format: Book
• Published: BMC, 2010-10-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>17α-Ethynyl-5-androsten-3β, 7β, 17β-triol (HE3286) is a synthetic derivative of an endogenous steroid androstenetriol (β-AET), a metabolite of the abundant adrenal steroid deyhdroepiandrosterone (DHEA), with broad anti-inflammatory activities. We tested the ability of this novel synthetic steroid with improved pharmacological properties to limit non-productive lung inflammation in rodents and attempted to gauge its immunological impact.</p> <p>Methods and Results</p> <p>In mice, oral treatment with HE3286 (40 mg/kg) significantly (<it>p </it>< 0.05) decreased neutrophil counts and exudate volumes (~50%) in carrageenan-induced pleurisy, and myeloperoxidase in lipopolysaccharide-induced lung injury. HE3286 (40 mg/kg) was not found to be profoundly immune suppressive in any of the classical animal models of immune function, including those used to evaluate antigen specific immune responses <it>in vivo </it>(ovalbumin immunization). When mice treated for two weeks with HE3286 were challenged with <it>K. pneumoniae</it>, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups.</p> <p>Conclusions</p> <p>HE3286 represents a novel, first-in-class anti-inflammatory agent that may translate certain benefits of β-AET observed in rodents into treatments for chronic inflammatory pulmonary disease.</p>

Item Description

10.1186/1476-9255-7-52
1476-9255