BRONCHOALVEOLAR CELL RESPONSE TO BACTERIAL CHALLENGE IN IMMUNOSUPPRESSED LUNG

Abstract

The effects of a 7-day course of 100 mg of cortisone acetate/kg of body wt per day plus 15 mg of cyclophosphamide/kg of body wt per day on bronchoalveolar cell kinetics was evaluated in a guinea pig model. On the day after the final dose of cortisone acetate and cyclophosphamide, normal and drug-treated animals underwent tracheobronchial lavage. Groups were lavaged before or 2 h after an intratracheal challenge with 1 .times. 108 colony-forming units of Pseudomonas aeruginosa administered in a saline suspension. Mean white blood cell counts were 4.46 .times. 103 cells/mm3 in normal animals and 1.93 .times. 103 cells/mm3 in drug-treated animals before Pseudomonas challenge; 11.7 .times. 103 cells/mm3 in normal animals and 1.55 .times. 103 cells/mm3 in drug-treated animals after challenge. Mean bronchoalveolar cell counts before challenge with Pseudomonas were 15 .times. 106 cells/lavage in normal animals and 8.8 .times. 106 cells/lavage in treated animals (P < 0.02). Pulmonary alveolar macrophages accounted for approximately 85% of cells in both groups. At 2 h after a Pseudomonas challenge, total bronchoalveolar cell counts were 8.44 .times. 106 cells/lavage in normal animals and 4.6 .times. 106 cells/lavage in the immunosuppressed group. In normal animals, the proportion of polymorphonuclear leukocytes increased from 5% of lavaged cells (0.75 .times. 106 polymorphonuclear leukocytes) before challenge, to 24% of cells (2.1 .times. 106 polymorphonuclear leukocytes) 2 h after challenge (P < 0.005). The drug-treated animals failed to show this polymorphonuclear leukocyte response to bacterial challenge (0.18 .times. 106 polymorphonuclear leukocytes after challenge). To evaluate pulmonary alveolar macrophage phagocytic and bactericidal capability after 7-day treatment with cortisone acetate and cyclophosphamide, lavaged pulmonary alveolar macrophages from normal and drug-treated animals were placed in cell culture and challenged with Pseudomonas labeled with 35S. Only high doses of cyclophosphamide (30 mg/kg per day) plus cortisone acetate (100 mg/kg pC day) were found to decrease pulmonary alveolar macrophage phagocytic capacity. A lower dose of cyclophosphamide (15 mg/kg per day) plus cortisone acetate did not. Intracellular killing was not decreased by these immunosuppressing drugs. Clinically relevant doses of 2 commonly used immunosuppressing drugs significantly decreased the numbers of bronchoalveolar macrophages and polymorphonuclear leukocytes available for a bacterial challenge, but the functional capability of pulmonary alveolar macrophages was only mildly affected by these drugs.