ORAL-ADMINISTRATION OF L-ARGININE POTENTIATES ALLERGEN-INDUCED AIRWAYINFLAMMATION AND EXPRESSION OF INTERLEUKIN-5 IN MICE

The role of nitric oxide in the airway hyperresponsiveness and inflamm ation of bronchial asthma has not yet been established. However, L-arg inine, the substrate for nitric oxide synthases, reportedly alleviates airway hyperresponsiveness caused by parainfluenza virus and reduces granulocytic inflammation induced by ischemia-reperfusion. We investig ated the effects of L-arginine on a murine model of allergic asthma th at included airway hyperresponsiveness, eosinophilic inflammation and expression of interleukin (IL)-5 in the lung. The mice received drinki ng water with or without L-arginine for 9 weeks. Histologic evaluation and cellular profiles in bronchoalveolar lavage fluid showed that p.o . administration of L-arginine (72 mu mol/kg/day) significantly enhanc ed eosinophilic airway inflammation and goblet cell proliferation that were associated with intratracheal instillation of ovalbumin. L-Argin ine also increased protein levels of IL-5 and IL-2 in supernatants fro m the lung exposed to ovalbumin. The number of eosinophils in bronchoa lveolar lavage fluid correlated significantly with the expression of I L-5. L-Arginine did not reverse ovalbumin-associated airway hyperrespo nsiveness to inhaled ACh. These results suggest that p.o. administrati on of L-arginine aggravates allergen-induced eosinophilic airway infla mmation via expression of IL-5, and in this model it does not show the rapeutic efficacy against airway hyperresponsiveness associated with a llergen exposure. Oral administration of L-arginine, the precursor of nitric oxide, may not be an effective intervention in allergic asthma.