INFLUENCE OF IMMUNOSUPPRESSION ON ALVEOLAR MACROPHAGE CHEMOTACTIC ACTIVITIES IN GUINEA-PIGS

Publisher Website
Google Scholar
Abstract
The increased risk of pneumonia associated with the administration of immunosuppressive drugs has prompted investigations of mechanisms for drug-induced pulmonary immunopathology. Pulmonary alveolar macrophages normally respond to chemotactic gradients and produce a chemotactic factor for polymorphonuclear leukocytes. A guinea pig model of immunosuppression was created, using week-long courses of cyclophosphamide, 15 mg/kg per day, or cortisone acetate 100 mg/kg per day to study the influences of immunosuppressive drugs on alveolar macrophage chemotactic behavior. N-formylmethionyl-leucyl-phenyl-alanine (f.cntdot.met.cntdot.leu.cntdot.phe), used at 10-8 M strength, was a potent chemotactic factor for macrophages lavaged from the lungs of normal animals. Pretreatment for 1 wk with cortisone resulted in a 60% reduction in alveolar macrophage responsiveness to f.cntdot.met.cntdot.leu.cntdot.phe (P < 0.02, t test). Cyclophosphamide treatment did not lead to chemotactic hyporesponsivensss in pulmonary alveolar macrophages. Alveolar macrophage tissue culture supernatants from normal and drug-treated animals were compared for the presence of macrophage-derived chemotactic factor. Both cortisone and cyclophosphamide drug regimens resulted in 25% reductions (P < 0.05) in chemotactic potency of the alveolar macrophage supernatants. Both cortisone acetate and cyclophosphamide treatment appear to adversely influence certain chemotactic activities of pulmonary alveolar macrophages.