Inhibition of chemokines prevents intraperitoneal adhesions in mice

BACKGROUND: The present study evaluates the efficacy of a broad-spectrumchemokine inhibitor, NR58-3.14.3, in the prevention of adhesionformation after i.p. surgery in mice. METHODS: A total of 110eight week old female Balb/c mice underwent laparotomy. Fortyanimals were randomly assigned to receive daily i.p. injectionsof either vehicle (control) or NR58-3.14.3. Time-course of adhesionformation was assessed. A titration of NR58-3.14.3 was conductedfor i.p. and s.c. administrations. The effectiveness of a singleintra-operative dose of NR58-3.14.3 was evaluated. Number, extent,location and type of adhesions were recorded. Immunohistochemistryof adhesions was done with leukocyte common antigen, CD45. RESULTS:Adhesion scores peaked on post-operative days 6–8. Onboth days 6 and 8, there were smaller adhesion size and lowercumulative adhesion scores in NR58-3.14.3-treated group. Moreover,on day 8, there were significantly fewer adhesions in NR58-3.14.3-treatedgroup compared to controls. The least effective dose for i.p.administration of NR58-3.14.3 was 0.45 mg/animal. Subcutaneousand single intra-operative i.p. administrations were also effectivein the prevention of i.p. adhesions. Although NR58-3.14.3 decreasedthe number of CD45⁺ inflammatory cells in the adhesions by 22.5%compared to control group, this was not significant. CONCLUSIONS:Our results show that this broad-spectrum chemokine inhibitorprevents post-operative adhesions in mice and may have a potentialclinical use.