Aminophylline-induced suppression of pulmonary antibacterial defenses

Respiratory infections are frequently observed in patients with chronic obstructive pulmonary disease, indicating that host defenses are compromised. Antibacterial defenses of the lung against such infections include the alveolar macrophage and polymorphonuclear leukocytes (PMN) that migrate into the lung to provide auxiliary phagocytic defenses. To test the hypothesis that aminophylline acutely impairs pulmonary antibacterial defenses, mice were challenged by aerosol inhalation with Staphylococcus aureus or Proteus mirabilis and injected intraperitoneally with aminophylline (20, 40, or 80 mg/kg). Pulmonary bactericidal activity and total lavaged lung cell and differential counts were determined 4 h after bacterial challenge. The highest dose of aminophylline suppressed the killing of S. aureus so that 55 ± 5% of the initial viable bacteria remained as compared with 22 ± 4% in the control animals. In contrast, there was a dose-related suppression of pulmonary antibacterial defenses against gram-negative bacteria. With doses of 40 and 80 mg/kg, lung defenses were ablated, allowing the proliferation of P. mirabilis to 115 ± 9% and 253 ± 9%, respectively, the control value being 26 ± 3%. The number of PMN obtained by lavage after aerosol challenge with P. mirabilis was also inhibited by aminophylline in a dose-dependent manner. From the lungs of untreated animals 5.0 ± 0.3 x 10⁶ PMN were recovered as compared with 3.3 ± 0.1 x 10⁶, 2.5 ± 0.2 x 10⁶, and 1.8 ± 0.1 x 10⁶, respectively, with increasing doses of aminophylline. The bactericidal activity of lavaged PMN from the lungs of aminophylline-treated rats challenged with the gram-negative bacterium in vivo was significantly depressed when compared with that in control animals. These studies show that aminophylline suppresses pulmonary antibacterial defenses by impairing the recruitment and bactericidal capacities of PMN responding to a bacterial challenge. Aminophylline may predispose patients to more frequent and severe infection.