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

Journal of Inflammation

Research

Anna M van Heeckeren¹  Ferdinando Nicoletti²  Katia Mangano²  Christopher L Reading³  Dwight Stickney³  James M Frincke³  Steven K White³  Dominick L Auci³  Raymond Pieters⁴  Angela Wang⁵  Douglas Conrad⁵ 

[1] Case Western Reserve University, School of Medicine, Pediatric Pulmonology, 10900 Euclid Avenue, 44106-4948, Cleveland, OH, USA;Department of Biomedical Sciences, School of Medicine,"Italic" Via Androne 83,95124, University of Catania, Catania, Italy;Harbor Biosciences, 9171 Towne Centre Drive, Suite 180, 92122, San Diego, CA, USA;IRAS-Immunotoxicology, Utrecht University, P.O. Box 80176, 3508, TD Utrecht, The Netherlands;VA San Diego Healthcare System, 3350 La Jolla Village Dr, 2161, San Diego, CA, USA;

关键词: Chronic Obstructive Pulmonary Disease;    Cystic Fibrosis;    Lung Inflammation;    Pleurisy;    Bacterial Burden;   

DOI  :  10.1186/1476-9255-7-52

 received in 2010-04-28, accepted in 2010-10-30,  发布年份 2010

来源: Springer

【 摘 要 】

Background17α-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.Methods and ResultsIn mice, oral treatment with HE3286 (40 mg/kg) significantly (p < 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 in vivo (ovalbumin immunization). When mice treated for two weeks with HE3286 were challenged with K. pneumoniae, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups.ConclusionsHE3286 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.

【 授权许可】

Unknown   
© Conrad et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.