Nicotinic stimulation of splenic T cells is protective in endoscopic retrograde cholangiopancreatography-induced acute pancreatitis in mice.

It has previously been shown that current smoking is protective against endoscopic retrograde cholangiopancreatography (ERCP)-induced acute pancreatitis, but the mechanism of this effect was not identified. We tested the hypothesis that nicotine is the active factor in this protection in a mouse model of ERCP. Pretreatment with nicotine dose dependently inhibited acute pancreatitis caused by infusion of ERCP contrast solution into the main pancreatic duct in mice. 3-2,4-Dimethoxybenzylidene anabaseine (GTS-21), a specific partial agonist of the α7 nicotinic cholinergic receptor (α7nAChR), also protected the pancreas against ERCP-induced acute pancreatitis. The effects of GTS-21 were abolished by pretreatment with the nicotinic receptor antagonist mecamylamine. Surgical splenectomy performed 7 days before ERCP-induced pancreatitis blocked the protective effects of GTS-21. Intravenous injection of a crude preparation of total splenocytes prepared from mice pretreated with GTS-21 inhibited ERCP-induced pancreatitis; splenocytes from mice treated with vehicle had no effect. When T cells were removed from the crude GTS-21-treated splenocyte preparation by immunomagnetic separation, the remaining non-T-cell splenocytes did not protect against ERCP-induced acute pancreatitis. We conclude that nicotine protects against ERCP-induced acute pancreatitis and that splenic T cells are required for this effect. Stimulation of α7 nicotinic cholinergic receptors may protect against ERCP-induced acute pancreatitis and may also be a novel approach to therapeutic reversal of ongoing acute pancreatitis.NEW & NOTEWORTHY Epidemiological evidence indicated that acute smoking reduced the risk of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis, but the mechanism has remained elusive. The current findings indicate the nicotine reduces the severity of ERCP-induced pancreatitis by stimulating a population of splenic T cells that exert a protective effect on the pancreas. These findings raise the possibility that nicotinic agonists might be useful in treating pancreatitis.

Duke Scholars

Author Michael Dee Gunn Medicine, Cardiology

Author Rodger Alan Liddle Medicine, Gastroenterology