Vol. 286, Issue 2, 767-771, August 1998

Oral Administration of L-Arginine Potentiates Allergen-Induced Airway Inflammation and Expression of Interleukin-5 in Mice

Hirohisa Takano , Heung-Bin Lim , Yuichi Miyabara, Takamichi Ichinose, Toshikazu Yoshikawa and Masaru Sagai

Research Team for Health Effects of Air Pollutants (H.T., H.-B.L., Y.M., T.I., M.S.), National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan, First Department of Medicine (H.T., T.Y.), Kyoto Prefectural University of Medicine, Kyoto, Japan and Korea Ginseng Tobacco Research Institute (H.-B.L.), Shinsung, Yunsung, Taejon, Korea.

The role of nitric oxide in the airway hyperresponsiveness and inflammation of bronchial asthma has not yet been established. However, L-arginine, the substrate for nitric oxide synthases, reportedly alleviates airway hyperresponsiveness caused by parainfluenza virus and reduces granulocytic inflammation induced by ischemia-reperfusion. We investigated the effects of L-arginine on a murine model of allergic asthma that included airway hyperresponsiveness, eosinophilic inflammation and expression of interleukin (IL)-5 in the lung. The mice received drinking 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 µmol/kg/day) significantly enhanced eosinophilic airway inflammation and goblet cell proliferation that were associated with intratracheal instillation of ovalbumin. L-Arginine also increased protein levels of IL-5 and IL-2 in supernatants from the lung exposed to ovalbumin. The number of eosinophils in bronchoalveolar lavage fluid correlated significantly with the expression of IL-5. L-Arginine did not reverse ovalbumin-associated airway hyperresponsiveness to inhaled ACh. These results suggest that p.o. administration of L-arginine aggravates allergen-induced eosinophilic airway inflammation via expression of IL-5, and in this model it does not show therapeutic efficacy against airway hyperresponsiveness associated with allergen exposure. Oral administration of L-arginine, the precursor of nitric oxide, may not be an effective intervention in allergic asthma.