Differential effects of cyclophosphamide and cortisone acetate on bronchoalveolar phagocytic cell populations

The effects of cyclophosphamide and cortisone acetate on numbers of pulmonary alveolar macrophages (PAM) and on inflammatory response of polymorphonuclear leukocytes to bacterial infection in the lung were studied in guinea pigs. Groups of animals were treated for 7 days with each drug alone or in combination. Bronchoalveolar lavage was carried out on the day after completion of the drug regimens. Selected animals were challenged via the trachea with Pseudomonas aeruginosa 2 hours before lavage. Single-drug therapy did not significantly decrease numbers of PAM in lavage fluids, but combined therapy led to a 60 per cent (P less than 0.01) decrease in numbers of PAM. Normal animals and cortisone-treated animals responded 2 hours after Pseudomonas lung challenge with a 4-fold increase in PMN in lavage fluid, wherease animals treated with cyclophosphamide or the combined-drug regimen failed in this response. The clearance of viable Pseudomonas organisms from bronchoalveolar fluids was inhibited only in animals treated with both cyclophosphamide and cortisone. Thus, only a combined regimen of cyclophosphamide plus cortisone led to the simultaneous occurrence of decreased numbers of PAM, as well as inhibition of polymorphonuclear leukocyte inflammation in the lung. Combined immunosuppressive drug regimens may result in more severe alterations in lung host defense for the clearance of bacteria than does single-drug therapy.