BRIEF EXPOSURE OF AIR-FILLED GUINEA-PIG ISOLATED TRACHEA TO LOW-LEVELS OF TOLUENE DIISOCYANATE (TDI) VAPOR IN-VITRO INCREASES REACTIVITY TOMETHACHOLINE

Toluene diisocyanate (TDI) causes occupational asthma characterized by inflammation and hyperreactivity of airways to irritants and bronchoc onstrictor drugs. We examined the non-immune, direct effect of TDI on airway reactivity in vitro in the absence of an inflammatory response using the guinea-pig isolated, perfused trachea preparation to measure reactivity to methacholine (MCh), and fixed point ion mobility spectr ometry to measure moment to moment levels of TDI vapor in air that was delivered to the tracheal mucosa. MCh was added to the mucosal modifi ed Krebs-Henseleit (MKH) perfusing solution to generate control concen tration-response curves for contractile responses. The lumen was then emptied and perfused with air or air containing 5, 20 or 70 ppb TDI va por, after which the trachea was perfused with MKH solution and reacti vity to MCh was re-examined. After only 30 min of treatment, TDI vapor concentration-dependently increased reactivity of the trachea to MCh (2.4- and 2.9-fold, respectively, for 20 and 70 ppb TDI; 5 ppb TDI and air alone had no effect). In tracheas treated in vitro with 2 mu M ca psaicin to deplete tachykinins, TDI caused the same (4-fold) increase in reactivity to MCh that was observed in control tracheas. However, T DI vapor (70 ppb) no longer enhanced reactivity to MCh in tracheas fro m which the epithelium had been removed. Our results indicate that a d irect, non-immune, non-inflammatory action of TDI on respiratory epith elium leads to hyperreactivity of airways in vitro. Published by Elsev ier Science Ireland Ltd.