Attenuation of airway hyperresponsiveness during acute viral infection using the 21-aminosteroid U-83836E in rats.
Respiratory viral infections have been associated with exacerbations of asthma in humans, and are known to produce airway obstruction and hyperresponsiveness in rats. Virus-induced airway dysfunction may result in part from inflammatory cells and their products, and agents that target these mechanisms might therefore attenuate viral airway injury. The 21-aminosteroid class of drugs has been reported to attenuate tissue injury in a variety of models, and we hypothesized that U-83836E, an orally-active aminosteroid, would prevent the development of airway dysfunction during acute viral illness. Adult rats were inoculated with either parainfluenza type 1 (Sendai) virus or sterile vehicle, treated with either U-83836E 20 mg/kg or water by oral gavage twice daily, and studied on postinoculation day 5, 6 or 7. Anesthetized, paralysed, mechanically ventilated rats were placed in a body plethysmograph for measurements of airway obstruction (resistance, dynamic compliance, eucapneic PaO2), and responsiveness to i.v. methacholine; lungs were lavaged to obtain inflammatory cells. The water-treated virus group was significantly different from the non-infected controls for all variables. Virus-induced hyperresponsiveness was attenuated (P = 0.027) by aminosteroid treatment, although airway obstruction and inflammation were not improved by the treatment. We conclude that 21-aminosteroids may protect airways from virus-induced hyperresponsiveness.
Sorkness
R
R
School of Pharmacy, University of Wisconsin-Madison 53792-3244, USA.
Lemanske
R F
RF
D000208:Acute Disease; D000402:Airway Obstruction / Q000188:drug therapy; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002839:Chromans / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008297:Male; D010879:Piperazines / Q000627:therapeutic use*; D051381:Rats; D018108:Respirovirus; D010253:Respirovirus Infections / Q000188:drug therapy*
D002839:Chromans; D016166:Free Radical Scavengers; D010879:Piperazines; C066382:U 78517F