Effect of methotrexate on asthmatic reaction in sensitized guinea pigs

To understand the mechanism of antiasthmatic property of the antimetabolite agent, methotrexate (MTX), we examined its effect on time-related changes in specific airway resistance, bronchial responsiveness, and accumulation of lymphocytes and eosinophils in lung tissue and the bronchial lumen, before and after antigen challenge in ovalbumin (OA)-sensitized guinea pigs. Intraperitoneal administration of MTX significantly inhibited the antigen-induced late asthmatic responses (LAR) in actively sensitized animals in dose-dependent manner. Examination of bronchoalveolar lavage fluid (BALF) revealed that 0.25, 0.5 and 1.0 mg/kg body weight of MTX significantly inhibited the recruitment of eosinophils, lymphocytes (6 and 24 h after antigen challenge) and neutrophils (0.5, 6 and 24 h after antigen challenge) in the airways in a dose-dependent manner. Histological examination of lung tissue revealed that MTX significantly inhibited eosinophil infiltration into the airway (6 and 24 h after antigen challenge). Furthermore, MTX significantly inhibited the infiltrations of PKH-2-labeled peripheral blood mononuclear cells (mostly lymphocytes) into the airways (24 h after antigen challenge). MTX also inhibited airway hyperresponsiveness to methacholine following OA challenge in a dose-dependent manner. We conclude that the antiasthmatic effect of methotrexate is mainly due to inhibition lymphocytes and eosinophil infiltration into the airway.