Background
Inflammatory events within the intestinal muscularis, including macrophage activation and leukocyte recruitment, have been demonstrated to participate in causing postoperative ileus. Recently, glycine has gained attention due to its beneficial immunomodulatory effects in transplantation, shock and sepsis.
Methods
Muscularis glycine receptors were investigated by immunohistochemistry. Gastrointestinal motility was assessed by in vivo transit distribution histograms with calculated geometric center analysis and jejunal circular smooth muscle contractility in a standard organ bath. The impact of glycine on the muscularis inflammatory responses to surgical manipulation of the intestine were measured by real-time PCR, nitric oxide Griess reaction, prostaglandin ELISA, Luminex and histochemistry. Key
Results
Glycine-gated chloride channels were immunohistochemically localized to muscularis macrophages and postoperative infiltrating leukocytes. Preoperative glycine treatment significantly improved postoperative gastrointestinal transit and jejunal circular muscle contractility. Preoperative glycine injection significantly reduced the induction of interleukin-6 (IL-6), tumor necrosis factor-α, inducible nitric oxide synthase and intercellular adhesion molecule-1 mRNAs, which was associated with the attenuation in postoperative leukocyte recruitment. Nitric oxide and prostanoid release from the postsurgical inflamed muscularis was diminished by glycine. The secretion of the inflammatory proteins IL-6, monocyte chemotactic protein-1/chemokine ligand 2 and macrophage inflammatory protein-1α/chemokine ligand 3 were also significantly decreased by glycine pretreatment. Conclusions & inferences: The data indicate that preoperative glycine reduces postoperative ileus via the early attenuation of primal inflammatory events within the surgically manipulated gut wall. Therapeutic modulation of resident macrophages by glycine is a potential novel pharmacological target for the prevention of postoperative ileus.