Anti-inflammatory effect of albuterol enantiomers during respiratory syncytial virus infection in rats.
Every year in the United States, respiratory syncytial virus (RSV) infections in infants and young children cause more than 120,000 hospitalizations, often complicated by the need for mechanical ventilation; yet no effective therapy is currently available for this disease. We showed previously that RSV infection is associated with neurogenic inflammation in the lower respiratory tract. In the present study, we sought to determine whether aerosolized beta(2)-receptor agonists inhibit neurogenic-mediated albumin extravasation in the airways of RSV-infected, mechanically ventilated rats, and to compare the anti-inflammatory effects of racemic albuterol ((RS)-albuterol) to its individual enantiomeric components (R)-albuterol and (S)-albuterol. Albumin extravasation evoked by sensorineural stimulation with capsaicin was inhibited only partially by 0.63 mg (RS)-albuterol, and higher doses had minimal incremental effects. In contrast, the anti-inflammatory effect of (R)-albuterol was already larger at the lowest dose of 0.31 mg, and complete inhibition of neurogenic exudation was observed at higher doses. (S)-albuterol had no significant inhibitory effect up to 1.25 mg, and had only partial inhibitory effect at higher doses. The anti-inflammatory effect of (R)-albuterol was independent from the expression of substance P neurokinin 1 receptors, suggesting a direct vascular effect. Our data show that (R)-albuterol has a much stronger inhibitory effect on neurogenic inflammation in RSV-infected airways when aerosolized in enantiomerically pure form, rather than in a racemic mixture with (S)-albuterol. Based on these data, we speculate that (R)-albuterol may be more effective than other adrenergic agents in the management of bronchiolitis.
Auais
Alexander
A
Department of Pediatrics, University of Miami School of Medicine, Miami, Florida 33136, USA.
Wedde-Beer
Katrin
K
Piedimonte
Giovanni
G
D000280:Administration, Inhalation; D000336:Aerosols; D000418:Albumins / Q000378:metabolism; D000420:Albuterol / Q000031:analogs & derivatives / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012121:Respiration, Artificial; D020545:Respiratory Mucosa / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000378:metabolism
D000336:Aerosols; D000418:Albumins; D000893:Anti-Inflammatory Agents; D005070:Evans Blue; D000420:Albuterol