Effect of leu-enkephalin analogue on the content of pro- and anti-inflammatory cytokines in the colonic wall in experimental ulcerative colitis

• Andrei Yu. Liashev
• Galina S. Mal’

Abstract

Introduction. The development of ulcerative colitis is associated with impaired immune homeostasis in the colonic wall, activation of CD8⁺IL-17⁺-cells, increased production of pro-inflammatory and impaired secretion of anti-inflammatory cytokines. The formation of immune inflammation leads to the development of infiltrates and ulcers, as well as crypts destruction. Considering the low efficiency of existing methods for the treatment of ulcerative colitis, the search for new treatments for inflammatory colonic diseases is an urgent task. Investigated leu-enkephalin analogue has a unique combination of pharmacological effects, including immunomodulatory effect.

The aim of study – investigation of leu-enkephalin analogue (Tyr-D-Ala-Gly-Phe-Leu-Arg) effect on the content of pro- and anti-inflammatory cytokines in the colonic wall in mice with experimental ulcerative colitis.

Material and methods. Ulcerative colitis in Balb/c mice was simulated by replacing drinking water with a 5 % solution of dextran sodium sulfate in boiled water for 5 days. On the 5^th, 7^th and 28^th days of the experiment, the content of IL-1β, IL-4, IL-6, IL-10 and IL-17 was measured in the homogenate of the medial section of the colon. The leu-enkephalin analogue was administered subcutaneously at a dose of 100 mcg/kg for 7 days.

Results. An increase in the content of IL-1β, IL-6, IL-10 and IL-17, as well as a decrease in the concentration of IL-4 in the colonic wall of mice of the control group with ulcerative colitis on the 5^th and 7^th days of the experiment was established. In chronic ulcerative colitis, only the concentration of IL-6 was significantly higher by 2.5 times than in naïve mice. The administration of leu-enkephalin analogue had an immunomodulatory effect: the content of proinflammatory cytokines decreased, while the content of Th2-cytokines increased during the acute period of the disease. In chronic ulcerative colitis, the administration of investigated peptide caused a decrease in the concentration of IL-6 and an increase in the content of IL-10 in the colonic wall.

Conclusion. The mechanism of leu-enkephalin analogue action on the content of inflammatory cytokines is apparently associated with the activation of opioid μ-receptors, which are widely present on the mononuclear cells of the colon wall, and whose expression increases in colonic inflammation development.

Keywords:ulcerative colitis; interleukins; leu-enkephalin analogue; opioid μ-receptors

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