The effect of treatment with the nonsteroidal anti-inflammatory agent piroxicam on leukocyte migration to the lungs was investigated after aerosol administration of sublethal doses of Pseudomonas aeruginosa to mice. Piroxicam decreased, in a dose-related fashion, the polymorphonuclear leukocyte recruitment to, and the degree of perivascular and peribronchial infiltration in, the lungs. Piroxicam treatment also protected the animals in a dose-dependent manner from challenge with lethal doses of P. aeruginosa. The effect of piroxicam was not related to direct action of the drug on the microorganisms. Piroxicam treatment maintained the animal's pulmonary defenses against infection while diminishing inflammatory responses against P. aeruginosa, an occurrence decreasing the potential for tissue damage due to phagocytes migrating from circulation.
Decreased lung clearance of Staphylococcus aureus has been reported in mice homozygous for the cribriform degeneration (cri) autosomal recessive mutation. In the present study, the phagocytic capacities of alveolar and peritoneal macrophages were quantitated by applying kinetics of the first order reaction criteria. The characteristics of the pulmonary and peritoneal mononuclear cell populations from mutant and control mice were indistinguishable. The kinetic assays revealed decreased phagocytosis work in both alveolar and peritoneal macrophages from cri/cri mice. The results lend support to this mutation as a possible model system to study the early stages of lung disease physiopathology in cystic fibrosis.
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