PULMONARY CATABOLISM OF INTERFERON-GAMMA EVALUATED BY LUNG PERFUSION OF BOTH NORMAL AND SMOKE-EXPOSED RATS

The role of the lungs in the catabolism of rat recombinant interferon- gamma, either in normal rats or in rats subjected to an acute cigarett e smoking episode, was evaluated using an isolated and perfused lung p reparation. After administration of zinterferon-gamma into the lung pe rfusion medium, there was no clearance of the cytokine in either contr ol 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 amou nt of interferon-gamma was instilled into the bronchial alveolar tree, concentrations of the cytokine in the perfusate increased progressive ly so that after 3 h up to 71.2 +/- 4.3 and 62 +/- 5.7% of the adminis tered dose, as measured by ELISA test, had been transferred from the b ronchial lumen to the perfusion medium of either control or smoke-expo sed rat lungs, respectively, the latter values being significantly low er (p less than or equal to 0.05) than those obtained in control lungs . Moreover, total recoveries of interferon-gamma evaluated in smoke-ex posed rat lungs (78.4 +/- 8.6%) were also significantly lower than tho se observed in control rat lungs (91.4 +/- 11.8%). Biologic activity e valuations on the same samples gave values significantly lower than th ose obtained using ELISA, indicating a partial loss of biologic activi ty during transalveolar transit, In conclusion, it appears that the tr ansfer of interferon-gamma is almost exclusively unidirectional from t he alveolar space to the plasmatic pool, with partial degradation duri ng transalveolar passage.