Inhibition of chemokines prevents intraperitoneal adhesions in mice.
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.
Berkkanoglu
Murat
M
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
Zhang
Lufang
L
Ulukus
Murat
M
Cakmak
Hakan
H
Kayisli
Umit A
UA
Kursun
Sinan
S
Arici
Aydin
A
D000818:Animals; D018925:Chemokines / Q000037:antagonists & inhibitors*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010532:Peritoneal Diseases / Q000473:pathology / Q000517:prevention & control*; D010537:Peritoneum / Q000601:surgery*; D011184:Postoperative Period; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control
D018925:Chemokines; D010456:Peptides, Cyclic; C411952:cyclo(cysteinyl-glutaminyl-isoleucyl-tryptophyl-lysyl-glutaminyl-lysyl-prolyl-aspartyl-leucyl-cysteinyl-amide)