Interstitial pulmonary fibrosis induced in hamsters by intratracheally administered chrysotile asbestos. Histology, lung mechanics, and inflammatory events.

The development of interstitial pulmonary fibrosis (IPF) is associated with persistent cellular infiltration and progressive connective tissue accumulation in the alveolar walls. To develop and characterize an animal model of IPF in which pulmonary fibrosis evolves slowly, as well as to develop an inexpensive, easily produced, model of asbestosis, Syrian golden hamsters received single intratracheal injections of either UICC chrysotile asbestos or saline. Animals were then examined at time points up to 180 days for pulmonary histologic and physiologic changes, cytologic characteristics of cells recovered by bronchoalveolar lavage, and spontaneous release of neutrophil chemoattractant activity by alveolar macrophages. Within days after asbestos treatment, hamsters developed a patchy bronchopneumonia centered around terminal airways, which progressed peripherally with time to involve the alveolar walls with persistent inflammation and the gradual development of interstitial and peribronchiolar fibrosis. These histologic changes were accompanied by physiologic findings of air-flow obstruction with air trapping. Bronchoalveolar lavage revealed a persistent neutrophilia that began within 24 h of asbestos treatment; this was associated with the spontaneous release of neutrophil chemotactic activity by cultured alveolar macrophages. In this animal model, pulmonary inflammation and fibrosis can be predictably produced by a single intratracheal instillation of chrysotile asbestos. It represents a useful tool for studying both asbestosis and pulmonary fibrosis in general.