Increased levels of surgical adhesions in TGF beta 1 heterozygous mice

Adhesion formation and fibrosis represent a major complication of surgical intervention. Reducing the morbidity associated with adhesions requires an understanding of the mechanisms underlying their formation. Since increased levels of transforming growth factor-beta 1 (TGF beta 1) have been associa ted with inflammation and adhesion production, we investigated the requirem ent of TGF beta 1 in peritoneal adhesion formation utilizing mice carrying a targeted disruption of the TGF beta 1 allele. Mice that were either wild- type (+/+), containing two normal alleles of TGF beta 1, or heterozygous (/-) for the TGF beta 1 null allele received injections of magnesium silicat e (talc), and the extent of abdominal adhesions was determined utilizing a standard grading score. Wild-type (+/+) animals had at least twofold more T GF beta 1 protein in peritoneal fluids at 2 h posttrauma compared to hetero zygous (+/-) mice (727 vs. 243 pg TGF beta 1/mg protein by enzyme-linked im munosorbent assay (ELISA) in +/+ and +/- mice, respectively), and had signi ficantly less scar and adhesion formation (p < .05) at 7 days posttrauma (1 .8 +/- 0.8 vs. 3.4 +/- 1.4, graded from 0 to 5, in +/+ and +/- mice, respec tively). These results demonstrate that haploid insufficiency in TGF beta 1 levels can lead to inappropriate matrix and adhesion production during inf lammation, and together with previous studies suggest that any perturbation of normal TGF beta 1 levels can modulate the injury response that regulate s the extent of adhesion formation.