ACCELERATION OF WOUND-HEALING IN GASTRIC-ULCERS BY LOCAL INJECTION OFNEUTRALIZING ANTIBODY TO TRANSFORMING GROWTH-FACTOR BETA(1)

Background-Application of neutralising antibodies (NAs) to transformin g growth factor beta(1) (TGF beta(1)) improves wound healing in experi mental glomerulonephritis and dermal incision wounds. TGF beta(1) has been detected in the stomach, but despite the fact that this cytokine plays a central part in wound healing no information is available to d etermine if modulation of the TGF beta(1) profile influences the heali ng of gastric ulcers. This study examines gastric ulcer healing in the rat after local injection of NAs to TGF beta(1). Method-Chronic gastr ic ulcers were induced in Wistar rats by the application of 100% aceti c acid to the serosal surface of the stomach. Immediately after ulcer induction and on day 2, NAs to TGF beta(1) (50 mu g), TGF beta(1) (50 mu g), saline or control antibodies (IgG; 50 mu g) were locally inject ed into the subserosa. Controls received no subserosal injections. Ani mals were killed on day 5 or 11, the ulcer area was measured planimetr ically, sections were embedded in paraffin wax, and stained with trich rome or haematoxylin and eosin. Depth of residual ulcer was assessed o n day 11 by a scale of 0-3, the percentage of connective tissue was de termined by a semiquantitative matrix score and granulocytes and macro phages in the ulcer bed were also assessed. Results-The application of NAs to TGF beta(1) led to a significant acceleration of gastric ulcer healing on day 11 (0.6 (SD 0.8) v 3.7 (SD 2.6) mm(2)), a reduction in macrophages (23.7 (SD 22.6) v 38 (26) per 40X power field) and granul ocytes (8.5 (SD 5.6) v 20 (10) per 40X power field), fewer histologica l residual ulcers (mean 1 (SD 0.9) v 2 (1 1)), a reduced matrix score, and a regenerative healing pattern. Excessive scarring was seen in th e TGF beta(1) treated group. Conclusion-Further treatment of gastric u lcers may induce a new treatment modality by local injection of NA to TGF beta(1) in an attempt to accelerate and improve ulcer healing.