Protease and protease inhibitor secretion by postsurgical macrophages following in vitro exposure to tolmetin.

Tolmetin sodium was shown previously to reduce the level of adhesions formed after peritoneal surgery. In addition, when tolmetin was administered to rats at the time of surgery, the level of macrophage activity (phagocytosis, superoxide anion production and tumoricidal activity) was elevated. In this study, the level of neutral protease activity in the culture supernatant of peritoneal macrophages from postsurgical rabbits. after in vitro exposure to tolmetin was examined. The level of collagenase, elastase and plasminogen activator inhibitor activity in the culture supernatant of macrophages was modulated after peritoneal surgery. Collagenase activity in the culture supernatant of macrophages from nonsurgical and postsurgical rabbits up to 48 h was reduced after co-culture with tolmetin. In contrast, elastase secretion was elevated to maximal levels (which plateaued 24 h after surgery in cultures of control macrophages) in cultures of macrophages from nonsurgical and early postsurgical (6 and 12 h) rabbits by in vitro exposure to tolmetin. Alternatively, the level of plasminogen activator inhibitor activity in the culture supernatants of postsurgical macrophages was reduced after in vitro exposure to tolmetin. These data indicate that tolmetin, a nonsteroidal anti-inflammatory agent, modulates the levels of collagenase, elastase and plasminogen activator inhibitor activity in culture supernatants of postsurgical macrophages.