Endogenous versus Exogenous IL-10 in Postoperative Intraperitoneal Adhesion Formation in a Murine Model

Abstract

Background: Modulation of the immune response to peritoneal injury may prevent postoperative adhesion formation. Exogenous interleukin-10 (IL-10) limits postoperative adhesion formation. The objective of the present study is to determine (I) the IL-10 dose most effective at adhesion prevention, (II) the presence of endogenous IL-10 in peritoneal fluid, and (III) the ability of an anti-IL-10 monoclonal antibody to modify postoperative intraperitoneal adhesion formation. Materials and methods: Within parts I, II, and III of the study 6-week-old Swiss Webster mice were randomized to have no surgery or to undergo a standardized adhesion-inducing peritoneal injury. Animals were further randomized to different dosing schedules of IL-10 (10 ng/kg to 100 μg/kg; part I), different times of euthanasia and peritoneal lavage after surgery (part II), or intraperitoneal (ip) treatment with phosphate-buffered saline vehicle (1 ml), IL-10 (1 μg/kg), or anti-IL-10 (1 μg/kg; part III). All ip injections were given immediately after surgery and then every 24 hr for a total of four injections. Animals were sacrificed 7 days after surgery and adhesion formation was assessed. Results: Maximal adhesion-limiting effects of exogenous IL-10 were reached at doses of 1 μg/kg. Mean detectable endogenous IL-10 levels in the peritoneal fluid varied from 145 to 220 pg/ml throughout the postoperative course. There were significant (P< 0.0005) differences in adhesion scores between mice treated with IL-10 (3.39; 95% CI 0.39–6.39) or PBS postoperatively (7.46; 95% CI 5.28–9.64), untreated surgical control animals (5.98; 95% CI 2.55–9.41), or anti-IL-10-treated animals (10.11; 95% CI 8.50–11.72). Conclusion: Interleukin 10 is effective at reducing postoperative intraperitoneal adhesion formation. Low levels of endogenous IL-10 are detectable in peritoneal fluid throughout the postoperative course, not correlating with adhesion scores. Anti-IL-10, when administered daily postoperatively in pharmacologic doses, does not appear to significantly increase postoperative adhesion formation. This puts into question if endogenous IL-10 production indeed plays a role in nonadhesiogenic peritoneal healing.