Formation of abdominal adhesions is inhibited by antibodies to transforming growth factor-beta1.
Transforming growth factor-beta (TGF-beta) is an important factor in regulating the inflammatory response and the production of extracellular matrix by fibroblasts. These two processes are linked in the formation of fibrous adhesions after abdominal surgery. When the mesothelium is injured a fibrin strand is produced which is populated first by inflammatory cells then by fibroblasts which secrete extracellular matrix forming a permanent adhesion. TGF-beta promotes both chemotaxis of monocytes 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 weeks 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 immediately 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 microgram per day), anti-TGF-beta (panspecific, 167 microgram per day), anti-TGF-beta1 (67 microgram per day), or anti-TGF-beta2 (50 microgram per day). The rats injected with anti-TGF-beta1 had significantly lower adhesion scores (P < 0.05) than the controls. Rats injected with anti-TGF-beta2 or anti-TGF-beta (panspecific) did not differ significantly from the control saline-injected rats. The results indicate that specifically reducing levels of TGF-beta1 alone can be effective in preventing abdominal adhesions.
Lucas
P A
PA
Surgical Section, Veterans Administration Medical Center, Castle Point, New York 12511, USA.
Warejcka
D J
DJ
Young
H E
HE
Lee
B Y
BY
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D004195:Disease Models, Animal; D008297:Male; D011183:Postoperative Complications / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000601:surgery; D000267:Tissue Adhesions / Q000517:prevention & control*; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000276:immunology*
D000906:Antibodies; D016212:Transforming Growth Factor beta