An inhibitor of cell proliferation associated with adhesion formation is suppressed by N,O-carboxymethyl chitosan

Surgical adhesions are a major cause of morbidity and mortality. The ideal barrier agent will both minimize adhesions and provide a milieu for the regeneration of the mesothelium lining of the abdominal and thoracic cavities. N,O-Carboxymethylchitosan (NOCC), a derivation of chitin that markedly reduces adhesions, may function to modulate intracellular signals such as growth factors and cytokines in the inflammatory exudate. Since transforming growth factor-beta is implicated in the fibrotic process, we investigated the possibility that NOCC's effects on adhesion formation reflects a modulation of TGF-beta activity. Using a biological assay for inhibition of cell proliferation to detect TGF-beta activity, we demonstrate that NOCC suppresses the levels of an inhibitor of cell proliferation released into serum and peritoneal exudates after cecal abrasion in the rat. However, this activity was distinct from known forms of TGF-beta as determined using both TGF-beta-neutralizing antisera and a TGF-beta-resistant cell proliferation assay. Thus at least one potential effect of NOCC involves a mechanism distinct from TGF-beta inhibition.