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The inhalation of isocyanates, such as toluene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), and hexamethylene diisocyanate (HDI) can induce hypersensitivity pneumonitis (HP) as well as bronchial asthma in humans, but the precise pathological features and their pathogenetic mechanisms have not been elucidated. To provide insight into the pathological features of isocyanate-induced hypersensitivity pneumonitis in humans, we repeatedly exposed guinea-pigs to TDI following previous sensitization to TDI and examined the inflammatory response in the pulmonary lesions. Following sensitization with 10% TDI ethyl acetate solution for seven consecutive days, guinea-pigs were exposed to 5% TDI ethyl acetate solution once a week for 4 weeks. As a control, guinea-pigs were exposed to ethyl acetate alone in the same manner. Furthermore, other guinea-pigs received a single exposure to 5 or 20% TDI ethyl acetate solution. The TDI solutions or ethyl acetate were applied to the bilateral nasal mucosa of guinea-pigs for 30 s-day-1. Histological examination of lung specimens of guinea-pigs repeatedly exposed to TDI after previous sensitization by TDI inhalation revealed interstitial pneumonitis-like lesions in which mononuclear cells and eosinophils were mainly involved. Lungs of control and nonsensitized guinea-pigs showed insignificant histological changes. We demonstrated that interstitial pneumonitis-like lesions, indistinguishable from isocyanate-induced hypersensitivity pneumonitis in humans, can be caused by repeated but not single exposure to TDI in guinea-pigs.

Interstitial pneumonitis-like lesions in guinea-pigs following repeated exposure to toluene diisocyanate