Cyclosporin A increases the pulmonary eosinophilia induced by inhaled Aspergillus antigen in mice.
We evaluated the effects of anti-inflammatory drugs in a murine model of allergic bronchopulmonary aspergillosis (ABPA). Mice instilled with 100 micrograms of Aspergillus fumigatus antigen (intranasally, 3 days a week for 3 weeks) developed pulmonary lesions, characterized by a perivascular and peribronchial eosinophil infiltration, a bronchoalveolar lavage (BAL) eosinophilia, and elevated levels of total IgE, total IgG1 and A. fumigatus-specific IgG1. Under the same conditions, groups of mice receiving a daily dose of 2 mg/kg dexamethasone showed decreased numbers of eosinophils and total cells in BAL, had less numerous eosinophils in their pulmonary infiltrates, and had lower levels of serum and BAL fluid total IgE, total IgG1 and A. fumigatus-specific IgG1. Conversely, groups of mice pretreated with an immunosuppressive agent, cyclosporin A (CsA) at a dose of 50 mg/kg, three times per week, developed pulmonary lesions with enhanced lung eosinophilic influx and increased total IgE levels, both in serum and in BAL fluid. These findings show that dexamethasone potently prevents the murine immunopathologic response to A. fumigatus. The effect of CsA on this inflammatory response was paradoxical, insofar as it suggests an activation of the T helper 2 subset, which up-regulates eosinophil recruitment and IgE production.
Wang
J M
JM
Unité de Recherche, Centre de Pneumologie de l'Hôpital Laval, Québec, Canada.
Denis
M
M
Fournier
M
M
Laviolette
M
M
D000280:Administration, Inhalation; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D000946:Antigens, Fungal / Q000633:toxicity*; D001232:Aspergillus fumigatus / Q000276:immunology*; D016572:Cyclosporine / Q000633:toxicity*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007136:Immunoglobulins / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D011657:Pulmonary Eosinophilia / Q000209:etiology*
D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D007136:Immunoglobulins; D003907:Dexamethasone; D016572:Cyclosporine