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

Abstract

The role of the lungs in the catabolism of tumor necrosis factor α (TNF-α) 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-α 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-α 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 <- 0.05) / than those obtained in control lungs. Moreover, total recoveries of TNF-α 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-α 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-α by aerosol.