Dexmedetomidine ameliorates TNBS-induced colitis by inducing immunomodulator effect

J Surg Res. 2013 Aug;183(2):733-41. doi: 10.1016/j.jss.2013.03.028. Epub 2013 Mar 31.

Abstract

Background: Since sedatives are often administered to immune-compromised and critically ill patients, our understanding of immunomodulation by sedation will be critical. Dexmedetomidine, a selective α2-adrenergic receptor agonist, is often used for sedation and analgesia especially in intensive care units. There are conflicting and little data concerning both the effect and the mechanism of dexmedetomidine on immune response. In our study, we aimed to investigate the effect of dexmedetomidine on immune system at two different doses (5 μg.kg(-1) and 30 μg.kg(-1)) during inflammatory bowel disease by using an experimental model, which resembles both systemic and local inflammation.

Methods: The effect of dexmedetomidine on the course of inflammatory bowel disease was investigated by measuring macroscopic and microscopic parameters. We investigated pro-inflammatory Th1, Th2, and Th17 cytokine levels in serum samples to analyze systemic immune response. Following this, local immune response was investigated by measuring cytokine levels in the presence of dexmedetomidine in spleen cell culture.

Results: Dexmedetomidine administration led to amelioration of all disease associated pathological manifestations. According to our in vitro and in vivo results, dexmedetomidine shows anti-inflammatory effect by increasing IL-4 and IL-10 levels responsible from anti-inflammatory response via Th2 pathway. Moreover, we showed for the first time in the study that dexmedetomidine administration reduces IL-23, which is responsible from initiation of inflammatory response via Th17 pathway.

Conclusions: Dexmedetomidine can have beneficial effect on preoperative or postoperative inflammatory bowel disease patients in intensive care units by down-regulating inflammatory immune response not only in systemic circulation but also in tissue-specific manner.

Keywords: Cytokines; Dexmedetomidine; Immune response; Inflammatory bowel diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use*
  • Animals
  • Cells, Cultured
  • Colitis / chemically induced*
  • Colitis / drug therapy*
  • Colitis / immunology
  • Cytokines / metabolism
  • Dexmedetomidine / pharmacology
  • Dexmedetomidine / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Immune System / drug effects
  • Immune System / physiology
  • Immunomodulation / drug effects
  • Immunomodulation / physiology*
  • In Vitro Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Spleen / drug effects
  • Spleen / metabolism
  • Spleen / pathology
  • Th17 Cells / pathology
  • Th2 Cells / pathology
  • Trinitrobenzenesulfonic Acid / adverse effects*

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Cytokines
  • Dexmedetomidine
  • Trinitrobenzenesulfonic Acid