Endogenous versus exogenous IL-10 in postoperative intraperitoneal adhesion formation in a murine model.
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.


METHODS
Within parts I, II, and III of the study 8-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 micrograms/kg; part I), different times of euthanasia and peritoneal lavage after surgery (part II), or intraperitoneal (i.p.) treatment with phosphate-buffered saline vehicle (1 ml), IL-10 (1 microgram/kg), or anti-IL-10 (1 microgram/kg; part III). All i.p. 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 exogenons IL-10 were reached at doses of 1 microgram/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).


CONCLUSIONS
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.
Holschneider
C H
CH
Department of Obstetrics and Gynecology, UCLA Center for Health Sciences 90095, USA.
Cristoforoni
P M
PM
Ghosh
K
K
Punyasavatsut
M
M
Abed
E
E
Montz
F J
FJ
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016753:Interleukin-10 / Q000494:pharmacology* / Q000502:physiology; D051379:Mice; D010532:Peritoneal Diseases / Q000209:etiology* / Q000517:prevention & control; D010537:Peritoneum / Q000601:surgery; D011184:Postoperative Period; D013997:Time Factors; D000267:Tissue Adhesions / Q000209:etiology* / Q000517:prevention & control
D016753:Interleukin-10