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 cigarette smoking episode, was evaluated using an isolated and perfused lung preparation. After administration of interferon-gamma 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-gamma 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 < or = 0.05) than those obtained in control lungs. Moreover, total recoveries of interferon-gamma 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-gamma is almost exclusively unidirectional from the alveolar space to the plasmatic pool, with partial degradation during transalveolar passage.
Pessina
G P
GP
Institute of General Physiology, University of Siena, Italy.
Paulesu
L
L
Corradeschi
F
F
Aldinucci
C
C
Luzzi
E
E
Bocci
V
V
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002263:Carboxyhemoglobin / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism* / Q000493:pharmacokinetics; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012906:Smoke / Q000009:adverse effects*
D011994:Recombinant Proteins; D012906:Smoke; D007371:Interferon-gamma; D002263:Carboxyhemoglobin