Pulmonary Catabolism of Interferon-γ Evaluated by Lung Perfusion of Both Normal and Smoke-Exposed Rats

The role of the lungs in the catabolism of rat recombinant interferon-γ, either in normal rats or in rats subjected to an acute cigarette smoking episode, was evaluated using an isolated and perfused lung preparation. After administration of interferon-γ into the lung perfusion medium, there was no clearance of the cytokine in either control or smoke-exposed rat lungs, and only 0.1 ± 0.2% of the total dose was recovered in the bronchoalveolar lavage fluid. When the same amount of interferon-γ was instilled into the bronchial alveolar tree, concentrations of the cytokine in the perfusate increased progressively so that after 3 h up to 71.2 ± 4.3 and 62 ± 5.7% of the administered dose, as measured by ELISA test, had been transferred from the bronchial lumen to the perfusion medium of either control or smoke-exposed rat lungs, respectively, the latter values being significantly lower (p ≤ 0.05) than those obtained in control lungs. Moreover, total recoveries of interferon-γ evaluated in smoke-exposed rat lungs (78.4 ± 8.6%) were also significantly lower than those observed in control rat lungs (91.4 ± 11.8%). Biologic activity evaluations on the same samples gave values significantly lower than those obtained using ELISA, indicating a partial loss of biologic activity during transalveolar transit. In conclusion, it appears that the transfer of interferon-γ is almost exclusively unidirectional from the alveolar space to the plasmatic pool, with partial degradation during transalveolar passage.