Acceleration of wound healing in gastric ulcers by local injection of neutralising antibody to transforming growth factor beta 1.

Abstract

Application of neutralising antibodies (NAs) to transforming growth factor beta 1 (TGF beta 1) improves wound healing in experimental 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 determine if modulation of the TGF beta 1 profile influences the healing of gastric ulcers. This study examines gastric ulcer healing in the rat after local injection of NAs to TGF beta 1. Chronic gastric ulcers were induced in Wistar rats by the application of 100% acetic acid to the serosal surface of the stomach. Immediately after ulcer induction and on day 2, NAs to TGF beta 1 (50 micrograms), TGF beta 1 (50 ng), saline or control antibodies (IgG; 50 micrograms) were locally injected into the subserosa. Controls received no subserosal injections. Animals were killed on day 5 or 11, the ulcer area was measured planimetrically, sections were embedded in paraffin wax, and stained with trichrome or haematoxylin and eosin. Depth of residual ulcer was assessed on day 11 by a scale of 0-3, the percentage of connective tissue was determined by a semiquantitative matrix score and granulocytes and macrophages in the ulcer bed were also assessed. 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) mm2), a reduction in macrophages (23.7 (SD 22.6) v 38 (26) per 40 x power field) and granulocytes (8.5 (SD 5.6) v 20 (10) per 40 x power field), fewer histological 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 the TGF beta 1 treated group. Further treatment of gastric ulcers may induce a new treatment modality by local injection of NA to TGF beta 1 in an attempt to accelerate and improve ulcer healing.