tailieunhanh - Báo cáo y học: "HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression. | Conrad et al. Journal of Inflammation 2010 7 52 http content 7 1 52 JOURNAL OF INFLAMMATION RESEARCH Open Access HE3286 an oral synthetic steroid treats lung inflammation in mice without immune suppression Douglas Conrad1 Angela Wang1 Raymond Pieters2 Ferdinando Nicoletti3 Katia Mangano3 Anna M van Heeckeren4 Steven K White5 James M Frincke5 Christopher L Reading5 Dwight Stickney5 Dominick L Auci5 Abstract Background 17a-Ethynyl-5-androsten-3b 7b 17P triol HE3286 is a synthetic derivative of an endogenous steroid androstenetriol b-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 Results In mice oral treatment with HE3286 40 mg kg significantly p 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. Conclusions HE3286 represents a novel first-in-class anti-inflammatory agent that may translate certain benefits of b-AET observed in rodents into treatments for chronic inflammatory pulmonary disease. Introduction Chronic obstructive pulmonary disease COPD a term most often used to describe chronic bronchitis and emphysema 1 2 is an inflammatory disease of the lungs marked by a loss of elastic recoil an increased resistance to airflow and decreased expiratory flow rate .