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Aminophylline-induced suppression of pulmonary antibacterial defenses
Abstract:
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 10(6) PMN were recovered as compared with 3.3 +/- 0.1 X 10(6), 2.5 +/- 0.2 X 10(6), and 1.8 +/- 0.1 X 10(6), 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Aminophylline significantly impairs pulmonary antibacterial defenses, particularly against gram-negative bacteria like Proteus mirabilis, by suppressing polymorphonuclear leukocytes (PMN) and reducing bacterial killing in mice.
Area of Science:
- Immunology
- Pulmonary Medicine
- Pharmacology
Background:
- Chronic obstructive pulmonary disease (COPD) patients are susceptible to respiratory infections due to compromised host defenses.
- Alveolar macrophages and polymorphonuclear leukocytes (PMN) are key cellular components of lung antibacterial immunity.
Purpose of the Study:
- To investigate the acute effects of aminophylline on pulmonary antibacterial defenses.
- To determine if aminophylline administration impacts the lung's ability to clear bacterial infections.
Main Methods:
- Mice were challenged with Staphylococcus aureus or Proteus mirabilis via aerosol inhalation.
- Mice received intraperitoneal injections of aminophylline at varying doses (20, 40, 80 mg/kg).
- Pulmonary bactericidal activity, lung lavage cell counts, and PMN differentials were assessed 4 hours post-challenge.
Main Results:
- Aminophylline suppressed the killing of S. aureus in a dose-dependent manner.
- Pulmonary defenses against P. mirabilis were significantly impaired, with bacterial proliferation observed at higher aminophylline doses.
- Aminophylline reduced the number of recruited PMN to the lungs and depressed their in vivo bactericidal activity.
Conclusions:
- Aminophylline acutely impairs pulmonary antibacterial defenses, especially against gram-negative bacteria.
- The drug's effects include reduced PMN recruitment and function, compromising the lung's ability to combat infection.
- These findings suggest caution in using aminophylline in patients with compromised respiratory function and high infection risk.