EFFECT OF ANTIBODY TO TRANSFORMING GROWTH-FACTOR-BETA ON BLEOMYCIN-INDUCED ACCUMULATION OF LUNG COLLAGEN IN MICE

Background-Increased production of transforming growth factor beta (TGF-beta) seems to have an important role in the pathophysiology of bleomycin induced lung fibrosis. This is attributed to the ability of TGF-beta 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-beta antibody in mice treated with bleomycin, which is a model of lung fibrosis. Under methoxyflurane anaesthesia, each mouse received intratracheally either 50 mul sterile isotonic saline or 0.125 units bleomycin in 50 mul. Within five minutes after the instillation, mice received into the tail vein 100 mul non-immune rabbit IgG, TGF-beta2 antibody, or a combination of TGF-beta2 and TGF-beta1 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 mug of TGF-beta2 antibody after instillation of bleomycin followed by 100 mug on day 5 and 100 mug on day 9 significantly reduced the bleomycin induced increases in the accumulation of lung collagen from 445.8 (42.3) mug/lung to 336.7 (56.6) mug/lung at 14 days. Similarly, the combined treatment with 250 mug TGF-beta2 antibody and 250 mug TGF-beta1 antibody after bleomycin instillation followed by 100 mug 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-beta has an important role in the aetiology of bleomycin induced lung fibrosis; the neutralisation of TGF-beta by systemic treatment with its antibodies offers a new mode of pharmacological intervention which may be useful in treating lung fibrosis.