Bleomycin-induced lung injury in the rabbit. Analysis and correlation of bronchoalveolar lavage, morphometrics, and fibroblast stimulating activity.

We have used a rabbit model of bleomycin-induced lung injury to evaluate the chronological changes in the bronchoalveolar lavage fluid (BALF) constituents. The correlation of these changes with morphologic alterations and measured soluble mediators of fibrosis has also been assessed. Three groups of 8 treated and 8 control New Zealand white rabbits received 10 U/kg bleomycin in normal saline, or equal volumes of saline intratracheally. The animals underwent bronchoalveolar lavage with a balloon tipped catheter localized to the right lower lobe at 3, 8, or 12 wk. Total cell counts and differentials were performed on the BALF. The lungs were examined histologically for inflammatory cells in the interstitium, alveoli, and airways by morphometric techniques. The lungs were also assayed for total hydroxyproline content. Bronchoalveolar lavage fluid supernatants and supernatants from lavaged macrophages cultured for 24 h were assayed for fibroblast stimulating activity (FSA) by 3H-thymidine incorporation into rabbit lung fibroblasts. There was a significant increase in macrophages and neutrophils in the BALF at 3 wk only, although the elevation of macrophages was sustained for longer than that of neutrophils. The numbers of BALF macrophages correlated with the morphometric assessment of the number of intra-alveolar macrophages (p less than 0.001) and interstitial mononuclear cells (p less than 0.001), as well as the extent of airway inflammation (p less than 0.001). The numbers of BALF neutrophils correlated with morphometrically assessed alveolar (p less than 0.01) and interstitial neutrophils (p less than 0.01) but not with any airway inflammation scores.(ABSTRACT TRUNCATED AT 250 WORDS)