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Hum. Reprod. Advance Access originally published online on July 8, 2005
Human Reproduction 2005 20(11):3047-3052; 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. For Permissions, please email: journals.permissions@oupjournals.org

Inhibition of chemokines prevents intraperitoneal adhesions in mice

Murat Berkkanoglu1, Lufang Zhang1, Murat Ulukus1, Hakan Cakmak1, Umit A. Kayisli1,2, Sinan Kursun1 and Aydin Arici1,3

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

3 To whom correspondence should be addressed at: Section of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT, 06520-8063, USA. E-mail: aydin.arici{at}yale.edu

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 intra-operative 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.

Key words: adhesion formation/chemokines/cytokines/murine model/peritoneum


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