Differential effects of (S)- and (R)-enantiomers of albuterol in a mouse asthma model.
J Allergy Clin Immunol
; 116(2): 332-40, 2005 Aug.
Article
en En
| MEDLINE
| ID: mdl-16083788
ABSTRACT
BACKGROUND:
(R)- and (S)-Enantiomers of albuterol likely exert differential effects in patients with asthma. The (R)-enantiomer binds to the beta2-adrenergic receptor with greater affinity than the (S)-enantiomer and is responsible for albuterol's bronchodilating activity. (S)-Albuterol augments bronchospasm and has proinflammatory actions.OBJECTIVE:
The study aim was to determine whether the (S)-enantiomer, in contrast to the (R)-enantiomer, has adverse effects on allergic airway inflammation and hyperresponsiveness in a mouse asthma model.METHODS:
Mice sensitized to ovalbumin (OVA) intraperitoneally on days 0 and 14 were challenged with OVA intranasally on days 14, 25, and 35. On day 36, 24 hours after the final allergen challenge, the effect of the (R)- and (S)-enantiomers of albuterol (1 mg x kg(-1) x d(-1) administered by means of a miniosmotic pump from days 13-36) on airway inflammation and hyperreactivity was determined.RESULTS:
In OVA-sensitized/OVA-challenged mice, (R)-albuterol significantly reduced the influx of eosinophils into the bronchoalveolar lavage fluid and airway tissue. (R)-Albuterol also significantly decreased airway goblet cell hyperplasia and mucus occlusion and levels of IL-4 in bronchoalveolar lavage fluid and OVA-specific IgE in plasma. Although (S)-albuterol significantly reduced airway eosinophil infiltration, goblet cell hyperplasia, and mucus occlusion, it increased airway edema and responsiveness to methacholine in OVA-sensitized/OVA-challenged mice. Allergen-induced airway edema and pulmonary mechanics were unaffected by (R)-albuterol.CONCLUSION:
Both (R)- and (S)-enantiomers of albuterol reduce airway eosinophil trafficking and mucus hypersecretion in a mouse model of asthma. However, (S)-albuterol increases allergen-induced airway edema and hyperresponsiveness. These adverse effects of the (S)-enantiomer on lung function might limit the clinical efficacy of racemic albuterol.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_asthma
/
6_other_respiratory_diseases
Asunto principal:
Asma
/
Agonistas Adrenérgicos beta
/
Albuterol
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Allergy Clin Immunol
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos