PULMONARY CATABOLISM OF INTERLEUKIN-6 EVALUATED BY LUNG PERFUSION OF NORMAL AND SMOKER RATS

Cytokines such as interleukin 6 are involved in the pulmonary inflamma tion arising as a result of smoking. By use of isolated and perfused l ung preparations we have evaluated the role of the lungs in the catabo lism of human recombinant interleukin 6 both in normal rats and in rat s subjected to an acute cigarette smoking episode. When interleukin 6 was incorporated into the lung perfusion medium, neither control nor s moke-exposed rat lungs cleared the cytokine and only 0 . 1 +/- 0 . 2% of the total dose was recovered in the bronchoalveolar lavage fluid. W hen, on the other hand, the same amount of interleukin 6 was instilled into the bronchoalveolar tree, concentrations of the cytokine in the perfusate increased progressively so that after 3 h up to 70 . 1 +/- 9 . 8% and 40 . 9 +/- 22 . 5% of the administered dose, as measured by immunoenzymatic test, had been transferred from the bronchial lumen to the perfusion medium of either control or smoker rat lungs, respectiv ely, indicating significantly (P less than or equal to 0 . 05) differe nt behaviour of the cytokine in the two experimental groups. Total rec overies of the administered interleukin 6 evaluated in smoke-exposed r at lungs were 55 . 3 +/- 23 . 2%, significantly lower than those for c ontrol rat lungs (83 . 9 +/- 11%). Determination of biological activit y gave values always lower than those measured by immunoenzymatic test , indicating loss of biological activity during the transalveolar tran sit. It appears that the transfer of interleukin 6, especially in smok ers, is almost exclusively unidirectional, from the alveolar space to the plasmatic pool with degradation during the transalveolar passage.