Biochemical and histological changes in pulmonary fibrosis induced in rabbits with intratracheal bleomycin

Pulmonary fibrosis was induced in rabbits by an intratracheal instillation of bleomycin. Histologically, at 2 weeks there was inflammation but only limited evidence of increased collagen deposition; at 8 weeks the inflammatory response had subsided and increased collagen deposition, characteristic of early interstitial fibrosis, was observed. Biochemical analyses showed bleomycin treatment caused marked increases in the total amounts of RNA, DNA, mixed protein, collagen and elastin when compared to controls (P less than 0.001 in all cases). Furthermore the increases were essentially complete by 2 weeks where the contents had increased by 110 +/- 13%, 60 +/- 11%, 148 +/- 12%, 94 +/- 15% and 89 +/- 11% respectively (P less than 0.001 in all cases). When collagen and elastin were expressed as concentrations with respect to wet weight, total protein or DNA content, the changes were not statistically significant. No changes were observed in the relative amounts of type I and type III collagen. It is concluded that: (1) compared to biochemical analysis, histology is relatively insensitive in detecting the early increases in connective tissue proteins; (2) measurements of lung collagen and elastin should be expressed as total lung contents wherever possible; the concentration of these proteins may remain unchanged, especially in the early stages of fibrosis, due to concomitant increases in other lung constituents; (3) changes in the relative amounts to types I and III collagens do not play a major role in the pathology of this form of pulmonary fibrosis.