Influence of immunosuppression on alveolar macrophage chemotactic activities in guinea pigs.
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, additionally, produce a chemotactic factor for polymorphonuclear leukocytes. A guinea pig model of immunosuppression was created, using week-long courses of cyclophosphamide, 15 mg per kg per day, or cortisone acetate, 100 mg per kg per day, to study the influences of immunosuppressive drugs on alveolar macrophage chemotactic behavior. N-formylmethionyl-leucyl-phenylalanine (f-met-leu-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, however, resulted in a 60% reduction in alveolar macrophage responsiveness to f-met-leu-phe (p less than 0.02, t test). In contrast, cyclophosphamide treatment did not lead to chemotactic hyporesponsiveness in pulmonary alveolar macrophages. In further studies, 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 less than 0.05) in chemotactic potency of the alveolar macrophage supernatants. Thus, both cortisone acetate and cyclophosphamide treatment appear to adversely influence certain chemotactic activities of pulmonary alveolar macrophages.
D000818:Animals; D002633:Chemotaxis / Q000187:drug effects*; D003348:Cortisone / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000166:cytology
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D003348:Cortisone