Serum-mediated relaxant response to toluene diisocyanate (TDI) in isolated guinea-pig bronchi

The present study was designed to evaluate whether pre-incubation with serum, obtained from both control and toluene diisocyanate (TDI)-immunized guinea-pigs, modified the contractile response to TDI in isolated guinea-pig bronchial rings. Guinea-pigs were anaesthetized and the main bronchi dissected in two rings. Bronchial rings were incubated with normal or immune serum (100 mul ml(-1) for 2h) and dose-response curves to TDI (0(.)03-1000 muM) were studied isometrically. Before serum incubation. in eight bronchial rings, epithelium was removed by rubbing the luminal surface gently with a gauze. In control rings. TDI produced a concentration-dependent contraction, whereas in rings pre-incubated with either normal or TDI-immune serum, it produced a concentration-dependent relaxation. Relaxation was 101(.)4 (SEM 17(.)4)% and 94(.)9 (SEM 21)% Of the relaxation induced by isoproterenol (1 mM) respectively with normal and TDI-immune serum. Similarly to the pre-incubation with serum, pre-incubation with albumin produced a concentration-dependent relaxation to TDI. Serum-induced relaxant response to TDI was not affected by capsaicin desensitization. it was only partially inhibited by an NK1-tachykinin antagonist, whereas it was blocked by indomethacin. In bronchial rings without epithelium, pre-incubated with serum. TDI caused contraction at highest doses. while it still induced relaxation at the lowest doses. This study shows that one or more components of the serum modify the contractile response to TDI in isolated guinea-pig bronchi. In bronchial rings without epithelium serum was able to inhibit the contration induced by low doses of TDI