Methylprednisolone impairs the bactericidal activity of alveolar macrophages

Corticosteroid treatment of patients following acid aspiration has been reported to increase the incidence of bacterial pneumonia, with Staphylococcus aureus being a common isolate. We hypothesized that administration of methylprednisolone (MP) to mice with acid-injured lungs would impair pulmonary clearance of S. aureus by compromising the bactericidal oxidative metabolism of pulmonary phagocytes. Using an inhalational bacterial challenge, we established that MP decreased pulmonary clearance of S. aureus. In mice with normal lungs and without MP treatment 14 +/- 2% of all initially deposited Staphylococci remained at 4 hr compared to 28 +/- 2% remaining in the lungs of mice with MP treatment. In mice with acid-injured lungs, MP caused a greater impairment of S. aureus clearance at 4 hr with 44 +/- 10% of all initially deposited bacteria remaining in the lungs of control mice and 210 +/- 24% remaining in the lungs of MP-treated mice. After it was demonstrated that there was no difference in the numbers of phagocytic cells obtained by lung lavage from mice with or without MP treatment, the bactericidal oxidative metabolism of these cells was quantitated using luminol-amplified chemiluminescence. Phagocytic cells from mice not exposed to S. aureus displayed minimal chemiluminescence whether they were treated with saline (22 +/- 14 mV) or MP (14 +/- 8 mV). In contrast, phagocytes from saline-treated mice exposed to S. aureus showed a significant increase in chemiluminescence (159 +/- 22 mV). Pretreatment with MP, however, prevented this response to S. aureus (21 +/- 13 mV), indicating that bactericidal oxidative metabolism of these phagocytic cells had been suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)