Role of transforming growth factor beta-1 in peritonitis-induced adhesions

Peritonitis is a major cause of intra-abdominal adhesion formation. The overexpression of transforming growth factor beta-1 (TGF-Beta1), a potent mitogen, chemoattractant, and stimulant for collagen synthesis by fibroblasts, has been linked to tissue fibrosis at various sites throughout the body including peritoneal adhesion formation. Hence we hypothesized that the mechanism(s) involved in peritonitis-induced adhesion formation may be mediated through the upregulation of TGF-Beta1 expression. Peritonitis was induced in rats by cecal ligation and puncture, while a control group underwent sham operation. Adhesions were scored and harvested from both groups at 0, 6 and 12 hours and at 1, 2, 4, 7, and 28 days. Tissue expression of TGF-Beta1 mRNA was determined by quantitative reverse transcription-polymerase chain reaction and TGF-Beta1 protein was localized by immunohistochemical analysis. Serum and peritoneal fluid TGF-Beta1 concentrations were quantified by enzyme-linked immunosorbent assay. Compared with sham operation, peritonitis was associated with a significantly greater incidence of abdominal adhesions and a significant increase in the levels of TGF-Beta1 mRNA expression at days 2, 4, and 7. Immunostaining intensity of TGF-Beta1 in adhesions from the peritonitis group also steadily rose through day 7. In peritoneal fluid, the ratio of active:total TGF-Beta1 was significantly increased in the peritonitis group on days 1, 2, and 4 compared with the sham group. These results suggest that peritonitis is associated with the upregulation of TGF-Beta1, a mechanism that may exacerbate adhesion formation.