Intraluminal fibrosis induced unilaterally by lobar instillation of CdCl2 into the rat lung

Lung injury induced by intratracheal instillation of cadmium chloride (CdCl2) into the rat lung may serve as a model of human interstitial lung disease. In this study, CdCl2 solutions were instilled through a lobar bronchus into the left lung of the rat. Two doses (400 micrograms or 50 micrograms of CdCl2, each in 400 microliters of neutral saline) were used and the morphologic changes occurring during the first 7 days after a single exposure were documented by light and electron microscopy. With the higher dose, inflammatory cells appeared in the alveolar interstitium 1 day after CdCl2 administration. Edema and thickening of the alveolar walls were evident, as were damaged type I epithelial cells and denuded basement membranes. Fibrin was found in the air spaces. Within 2 days, inflammatory cells were seen in large numbers and fibroblasts were observed passing through gaps in the alveolar basement membranes into the air spaces. By 4 and 7 days after CdCl2, various forms of intraluminal fibrosis, including intrabronchiolar budding, mural incorporation, and obliterative changes, were observed. The contralateral lungs had normal-appearing architecture for all the time points investigated. In the lower dose exposure, gradients of alveolar damage were observed in which normal lung, interstitial fibrosis, and/or intraluminal fibrosis were seen within treated lungs. In the mildly damaged regions, interstitial fibrosis predominated, while in the more severely damaged regions, mural incorporation of the convoluted basement membranes was observed. The pulmonary fibrosis that developed appeared to be similar to some human interstitial lung diseases and may offer a system in which to study the regulation of collagen deposition and fibrosis development in these pathologic conditions.