Nicotinic Stimulation of Splenic T Cells is Protective in ERCP-induced Acute Pancreatitis in Mice.

Pretreatment with nicotine dose-dependently inhibited acute pancreatitis caused by infusion of ERCP contrast solution into the main pancreatic duct in mice. 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 prior to 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 splenic T cells are required for nicotinic protection against ERCP-induced acute pancreatitis and that stimulation of α7 nicotinic cholinergic receptors may protect against ERCP-induced acute pancreatitis and also provide a novel approach to therapeutic reversal of ongoing acute pancreatitis.