AIRWAY HYPERREACTIVITY ELICITED BY TOLUENE DIISOCYANATE (TDI)-ALBUMINCONJUGATE IS NOT ACCOMPANIED BY AIRWAY EOSINOPHILIC INFILTRATION IN GUINEA-PIGS

Nonspecific airway hyperresponsiveness is present in many patients wit h toluene diisocyanate (TDI)-induced asthma; however, the underlying p athophysiological mechanisms of this hyperresponsiveness remain contro versial. In the present study, we used a guinea pig model to investiga te the association of TDI-induced airway hyperresponsiveness with eosi nophilic airway infiltration, which is widely considered to play a key role in the development of allergen-induced hyperresponsiveness. Guin ea pigs were sensitized by i.d. injections of 10 mu l TDI on day 1 and day 6. Control animals received saline injections. Two weeks after th e second injection, airway reactivity to inhaled methacholine and spec ific airway resistance (sR(aw)) was measured before and at several tim es after inhalation challenge with TDI-GSA (guinea pig serum albumin) conjugates. Eosinophils in the airways were detected using enzyme hist ochemistry and quantified using computer-assisted image analysis. TDI- specific IgG(1) antibodies were found in the blood of TDI-sensitized a nimals. An immediate increase in sR(aw) was induced in these animals b y TDI-GSA challenge; airway hyperresponsiveness to methacholine was ob served at 6 h and 18 h after TDI-GSA challenge. However, TDI-GSA chall enge did not result in an elevation of eosinophils in the airways, com pared with control animals. The results suggest that the development o f TDI-induced airway hyperresponsiveness is not dependent upon eosinop hil infiltration in airways.