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.
Gonokami
Y
Y
First Department of Internal Medicine, School of Medicine, Showa University, Tokyo, Japan.
Konno
S I
SI
Kurokawa
M
M
Adachi
M
M
D000403:Airway Resistance / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001980:Bronchi / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004804:Eosinophils / Q000166:cytology; D006168:Guinea Pigs; D007114:Immunization; D008168:Lung / Q000166:cytology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D012137:Respiratory System / Q000473:pathology; D013997:Time Factors
D008727:Methotrexate