FORMATION OF ABDOMINAL ADHESIONS IS INHIBITED BY ANTIBODIES TO TRANSFORMING GROWTH-FACTOR-BETA

Transforming growth factor-beta (TGF-beta) is an important factor in r egulating the inflammatory response and the production of extracellula r matrix by fibroblasts. These two processes are linked in the formati on of fibrous adhesions after abdominal surgery. When the mesothelium is injured a fibrin strand is produced which is populated first by inf lammatory cells then by fibroblasts which secrete extracellular matrix forming a permanent adhesion. TGF-beta promotes both chemotaxis of mo nocytes and the production of extracellular matrix by fibroblasts. We have used a model of abdominal adhesions in rats in which a circle of peritoneum is dissected and then sutured into place again. After 2 wee ks the rats are euthanized and the adhesions are scored. Six groups of 10 rats each underwent this surgery. Group I served as the operative control. Group II was treated with saline which was injected immediate ly after surgery and on Days 1 and 2 after surgery (vehicle control). Using the same protocol with saline as vehicle, the other four groups of rats were treated with nonspecific IgG (150 mu g per day), anti-TGF -beta (panspecific, 167 mu g per day), anti-TGF-beta 1 (67 mu g per da y), or anti-TGF-beta 2 (50 mu g per day). The rats injected with anti- TGF-beta 1 had significantly lower adhesion scores (P < 0.05) than the controls. Rats injected with anti-TGF-beta 2 or anti-TGF-beta (panspe cific) did not differ significantly from the control saline-injected r ats. The results indicate that specifically reducing levels of TGF-bet a 1 alone can be effective in preventing abdominal adhesions. (C) 1996 Academic Press, Inc.