Pharmacologic stimulation of the nicotinic anti-inflammatory pathway modulates gut and lung injury after hypoxia-reoxygenation injury

• Published in: Surgery 2013-10, Vol.154 (4), p.841-848
• Main Authors: Tarras, Samantha L., MD, Diebel, Lawrence N., MD, Liberati, David M., MS, Ginnebaugh, Kevin, BS
• Format: Article
• Language: English
• Subjects: Bridged-Ring Compounds - pharmacology; Cell Hypoxia; HT29 Cells; Humans; Interleukin-6 - analysis; Intestines - blood supply; Intestines - metabolism; Lung Injury - prevention & control; Nicotine - pharmacology; Reperfusion Injury - prevention & control; Spiro Compounds - pharmacology; Surgery; Tumor Necrosis Factor-alpha - analysis; Vagus Nerve - physiology
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2013.07.018

Purpose Pre-injury vagal nerve stimulation protects against gut and lung injury after experimental hemorrhagic shock (HS). This likely occurs via the cholinergic anti-inflammatory pathway and the α7 nicotinic acetylcholine receptor (α7nAChR). We hypothesized that, in an in vitro model, either nicotine or a selective α7nAChR agonist (AR-R17779) would modulate intestinal and pulmonary effects of gut ischemia-reperfusion after hypoxic insult. Methods Confluent HT29 intestinal epithelial cells were co-cultured with Escherichia coli. Cell cultures were subjected to 21% (control) or 5% O2 (hypoxia) for 90 minutes followed by reoxygenation (H/R). HT29 cells were treated with nicotine or AR-R17779 before or immediately after hypoxic insult. From the HT29 cell culture supernatants, tumor necrosis factor-α and interleukin-6 levels were quantitated. Confluent pulmonary microvascular epithelial cells (HMVEC) were co-cultured with HT29 supernatants and permeability and intercellular adhesion molecule-1 expression were determined. Results In post H/R insult treatments with the receptor agonist, cytokine levels in HT29 cells were reduced to control levels. In HMVEC experiments, a protective effect was seen with treatment post H/R injury. Disruption of HT29 actin microfilaments was demonstrated after H/R insult and was abrogated by both agonists. Conclusion Post-insult pharmacologic stimulation seems to mimic the protective effects of pre-HS vagal nerve stimulation seen in animal studies.