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Hum. Reprod. Advance Access published online on July 8, 2005
Human Reproduction, doi:10.1093/humrep/dei182
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Received January 26, 2005
Revised April 27, 2005
Accepted June 9, 2005

Article

Inhibition of chemokines prevents intraperitoneal adhesions in mice

Murat Berkkanoglu 1, Lufang Zhang 1, Murat Ulukus 1, Hakan Cakmak 1, Umit A. Kayisli 2, Sinan Kursun 1, and Aydin Arici 1*

1 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
2 Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA and Department of Histology and Embryology, Akdeniz University School of Medicine, Antalya, 07070, Turkey

* To whom correspondence should be addressed.
Aydin Arici, E-mail: aydin.arici{at}yale.edu


  Abstract

BACKGROUND: The present study evaluates the efficacy of a broad-spectrum chemokine inhibitor, NR58-3.14.3, in the prevention of adhesion formation after i.p. surgery in mice. METHODS: A total of 110 eight week old female Balb/c mice underwent laparotomy. Forty animals were randomly assigned to receive daily i.p. injections of either vehicle (control) or NR58-3.14.3. Time-course of adhesion formation was assessed. A titration of NR58-3.14.3 was conducted for i.p. and s.c. administrations. The effectiveness of a single intra-operative dose of NR58-3.14.3 was evaluated. Number, extent, location and type of adhesions were recorded. Immunohistochemistry of adhesions was done with leukocyte common antigen, CD45. RESULTS: Adhesion scores peaked on post-operative days 6-8. On both days 6 and 8, there were smaller adhesion size and lower cumulative adhesion scores in NR58-3.14.3-treated group. Moreover, on day 8, there were significantly fewer adhesions in NR58-3.14.3-treated group compared to controls. The least effective dose for i.p. administration of NR58-3.14.3 was 0.45 mg/animal. Subcutaneous and single intraoperative i.p. administrations were also effective in the prevention of i.p. adhesions. Although NR58-3.14.3 decreased the 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 inhibitor prevents post-operative adhesions in mice and may have a potential clinical use.

Keywords: adhesion formation/chemokines/cytokines/murine model/peritoneum.
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