Effect of antibody to transforming growth factor /B on bleomycin induced accumulation of lung collagen in mice

Background-Increased production of transforming growth factor p (TGF-β) seems to have an important role in the pathophysiology of bleomycin induced lung fibrosis. This is attributed to the ability of TGF-β to stimulate infiltration of inflammatory cells and promote synthesis of connective tissue, leading to collagen deposition. Methods-The study was designed to evaluate the antifibrotic potential of TGF-β antibody in mice treated with bleomycin, which is a model of lung fibrosis. Under methoxyflurane anaesthesia, each mouse received intratracheally either 50 μl sterile isotonic saline or 0.125 units bleomycin in 50 μl. Within five minutes after the instillation, mice received into the tail vein 100 μl non-immune rabbit IgG, TGF-β antibody, or a combination of TGF-β and TGF-β antibodies at various dose regimens. Mice were killed 14 days after the instillation and their lungs processed for morphological and biochemical studies. Results-Administration of 250 μg of TGF-β antibody after instillation of bleomycin followed by 100 μg on day 5 and 100 μg on day 9 significantly reduced the bleomycin induced increases in the accumulation of lung collagen from 445 8 (42.3) μg/lung to 336-7 (56.6) μg/lung at 14 days. Similarly, the combined treatment with 250 μg TGF-β antibody and 250 μg TGF-β1 antibody after bleomycin instillation followed by 100 μg of each antibody on day 5 also caused a significant reduction in bleomycin induced increases in lung collagen accumulation and myeloperoxidase activity at 14 days. Conclusions-These results suggest that TGF-β has an important role in the aetiology of bleomycin induced lung fibrosis; the neutralisation of TGF-β by systemic treatment with its antibodies offers a new mode of pharmacological intervention which may be useful in treating lung fibrosis.