Pharmacokinetics and catabolism of tumor necrosis factor-alpha in rat lungs

The role of the lungs in the catabolism of tumor necrosis factor alpha (TNF-alpha) either in normal rats, or in rats subjected to an acute cigarette smoking episode has been evaluated by using isolated and perfused lung preparations. After administration of TNF-alpha into the lung perfusion medium, there was no clearance of the cytokine in both control and smoker rat lungs and only 0.2 +/- 0.1% of the administered dose was recovered in the bronchoalveolar lavage fluid. When TNF-alpha was instilled into the bronchoalveolar tree, concentrations of the cytokine in the perfusate increased progressively so that after 3 h up to 68.8 +/- 8% and 52.7 +/- 11.4% of the administered dose had been transferred from the bronchial lumen to the perfusion medium of either control or smoker rat lungs, respectively, the latter values being significantly lower (p < or = 0.05) than those obtained in control lungs. Moreover, total recoveries of TNF-alpha evaluated in smoker rat lungs (65.5 +/- 10.2%) were also significantly lower than those observed in control rat lungs (82.8 +/- 7.1%). In conclusion, it appears that transfer of TNF-alpha is almost exclusively unidirectional, from the alveolar space to the plasma pool with partial degradation during the transalveolar passage. These results may be useful when attempting to deliver TNF-alpha by aerosol.