Effects of an Interferon Inducer Bropirimine on Bleomycin‐Induced Lung Fibrosis in Hamsters*

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Abstract
The antifibrotic effect of an interferon inducer, bropirimine (2‐amino‐5‐bromo‐6‐phenyl‐4(3H)‐pyrimidinone, ABPP) was evaluated in bleomycin (BLM)‐hamster model of lung fibrosis. ABPP is an orally active biological response modifier and has immunomodulatory, antiviral, and antineoplastic activities. The hamsters were randomized in four groups and treated with either bropirimine (100 mg/kg, intraperitoneally) suspended in carboxymethylcellulose (CMC, 10 mg/10 mg/ml) or CMC alone each day for sixteen days. After two days, the hamsters received either single bolus of BLM (7.5 U/5 ml/kg) or an equivalent volume of saline by the transoral endotracheal route. Groupings were assigned as: CMC + saline (CS), ABPP + saline (AS), CMC + BLM (CB) and ABPP + BLM (AB). Animals were sacrificed at fourteen days after intratracheal installation of either BLM or saline. Their lungs were lavaged and processed for morphometric and biochemical studies. ABPP had little effect in preventing BLM‐induced weight loss and lung injury. ABPP was found to reduce the BLM‐induced accumulation of collagen in the lung as measured by hydroxyproline content. The hamsters in AB group had significantly less collagen than the hamsters in CB group: 995 and 1157 μg hydroxyproline/lung, respectively. Administration of ABPP prevented the BLM‐induced increase in the lung prolyl hydroxylase activity. The total number of monocytes and eosinophils recovered from the bronchoalveolar lavage fluid (BALF) of the AB group were significantly lower than that of the animals in CB group. However, the BALF supernatant protein content from animals in AB group (7.9 mg/lung) was significantly higher than that of CB group (4.5 mg/lung). There were no differences in morphometric estimates of the volume of parenchymal lesions and total number of cells recovered in the BALF between CB and AB groups. Results of this study suggest that ABPP has an inhibitory effect on collagen accumulation, and monocyte and eosinophil infiltration, but it potentiates BLM‐induced increases in the pulmonary vascular permeability.