Effect of anti-adhesion agents on cytokine profile in an experimental model of postoperative intra-abdominal adhesions

Abstract

Many attempts have been made to prevent peritoneal adhesions using anti-adhesion agents, barriers and other therapeutic approaches, but their efficacy has not been widely accepted.

Purpose – to determine the effects of mezogel, a mixture of metronidazole, dextran, and contrykal enriched with oxygen based on the pro- and anti-inflammatory cytokine concentration in rats with simulated postoperative peritoneal adhesions.

Materials and methods. A total of 90 outbred white rats, divided into three groups of 30 animals each, underwent laparotomy and mechanical injury of the small bowel wall until a drop of blood appeared. After mechanical injury of the small bowel wall, the abdominal wound in group 1 animals (control) was closed with a layered suture technique; group 2 animals (comparison) were administered one mL of mezogel into the abdominal cavity before layer-by-layer suturing; group 3 animals (experimental) were introduced one mL of a specially prepared mixture of metronidazole, dextran, and contrykal (in a ratio of 1:1:0.1, respectively) enriched with oxygen into the abdominal cavity before the laparotomy wound was closed. Each surgical intervention lasted 15–20 minutes. On days 5, 10 and 21 of the experiment interleukin (IL) 4, IL-6, IL-10 and tumour necrosis factor alpha (TNF-α) were determined in the blood by enzyme immunoassay using corresponding test kits manufactured by Bender Medsystems (Austria).

Results. The levels of the anti-inflammatory cytokines IL-4 and IL-10 increased dynamically in groups 2 and 3, while group 1 showed their decrease. The proinflammatory cytokine IL-6 and TNF-α concentration decreased in the experimental and comparison groups during the study period. On day 5 in groups 2 and 3, compared to group 1, the IL-6 concentration was reduced by 28.4% (p=0.029) and 41.0% (p=0.006), respectively. Group 3 animals had a 17.6% (p=0.043) lower IL-6 level compared to group 2 animals. On days 10 and 21 a dynamic decrease in IL-6 was observed in the animals of groups 2 and 3. Group 3 animals had the lowest TNF-α, 41.9 % (p=0.001) lower than in group 1, and 31.7 % (p=0.118) lower than in group 2. There were significant strong relationships detected between IL-10 and IL-6 in all groups on day 5 of the study.

Conclusions. The administration of anti-adhesion agents, mezogel and an oxygen-enriched mixture of metronidazole, dextran, and contrykal, inhibits inflammation, which is expressed as a decrease in the concentrations of IL-6 and TNF-α. These agents lead to a negative interaction of anti-inflammatory cytokines with pro-inflammatory cytokines, in particular IL-4 with IL-6 and IL-10 with IL-6, indicating a greater prophylactic effect.

The experiments with laboratory animals were provided in accordance with all bioethical norms and guidelines.

No conflict of interests was declared by the authors.