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. Author manuscript; available in PMC: 2015 Aug 18.
Published in final edited form as: J Intern Med. 2009 Jun;265(6):663–679. doi: 10.1111/j.1365-2796.2009.02098.x

Table 1.

Effect of vagus nerve stimulation and selective α7 agonists in experimental models of inflammatory disease

Model Vagus nerve stimulation (VNS) or vagotomy α7 Agonist or antagonist
Endotoxaemia VNS: Reduced liver and serum TNF prevented shock [15] Nicotine patch: Attenuated fever and increased mean arterial pressure in humans injected with endotoxin. No significant effect on circulating TNF, IL-6, IL-8 nor soluble E-selectin. Increased circulating IL-10 and cortisol [123]
GTS-21: Improved survival. Reduced serum TNF [46]
GTS-21: Reduced serum TNF. Decreased neutrophil recruitment to peritoneum through an effect independent of TNF, KC and MIP-2. Did not alter serum IL-10 [47]
VNS: Reduced TNF in heart [122]
VNS: Decreased mRNA TNF in spleen. Reduced liver and spleen TNF [19]
Vagotomy: Increased serum and liver TNF [15]
Transcutaneous VNS: Reduced serum TNF [17]
VNS: Reduced procoagulant response and fibrinolytic response. Reduced serum TNF and IL-6. Reduced TNF, IL-1β and IL-6 in spleen. No effect on serum and spleen IL-10 [44]
Sepsis (cecal ligation and puncture) Transcutaneous VNS: Reduced serum HMGB1 levels and improved survival [17] Nicotine: Attenuated serum HMGB1. Improved survival [45]
GTS-21: Improved survival. Reduced serum HMGB1 [46]
AChE inhibitors: Improved survival (physostigmine and neostigmine). Reduced serum TNF, IL-1β and IL-6 (physostigmine) [101]
Sepsis (intraperitoneal injection of E. coli) Vagotomy: Increased TNF, IL-1β and IL-6 in serum and peritoneum. Increased granulocyte and macrophage counts in peritoneum [41] Nicotine: Reduced serum TNF, IL-1β and IL-6 in serum and peritoneum. Reduced granulocyte and macrophage counts in peritoneum. Reduced serum ALT and AST. Facilitated E. coli growth in peritoneal lavage fluid, blood and liver and accelerated mortality [41]
Sepsis (ascendent colon stent peritonitis) Vagotomy: Increased mortality. Increased serum TNF, IL-6, IL-10 and MCP-1 [42]
Postoperative ileus VNS: Prevented gastroparesis induced by intestinal manipulation. Reduced Ccl 2 and Ccl 3 mRNA in muscularis tissue. Reduced TNF, IL-6, MIP-2 and MIP-1α concentration in the peritoneal cavity. Reduced inflammatory cell recruitment to the intestinal muscularis. Activated STAT3 in resident macrophages of the intestinal muscularis [61] Nicotine: Reduced TNF and IL-6 production by peritoneal macrophages. AR-R17779: Improved gastric emptying. Reduced inflammatory cell recruitment to intestinal muscle [62]
Pancreatitis Vagotomy: Increased plasma amylase and lipase. Increased pancreatitis severity [49] Mecamylamine: Increased pancreatitis severity GTS-21: Attenuated pancreatitis severity [49]
Schwartzman reaction Nicotine: Reduced VCAM and E-selectin mRNA [63]
Carrageenan air pouch model Nicotine: Reduced inflammatory cell infiltration into the pouch [63] Nicotine: Reduced inflammatory cell infiltration into the pouch. Reduced TNF and MCP-1 content in the pouch [63]
Haemorrhagic shock VNS: Attenuated NF-κB activation and prevented IκBα loss in the liver. Decreased TNF mRNA and serum TNF. Reverted hypotension and prolonged survival time [53]
ACTH-mediated activation of vagus nerve: Decreased NF-κB activity and TNF mRNA in liver. Decreased serum TNF. Improved cardiovascular and pulmonary function and increased survival [56]
High-fat diet-induced activation of vagus nerve: Decreased serum TNF and IL-6. Preserved intestinal barrier function [57]		 Chlorisondamine: Reverted the effects of vagus nerve stimulation [53]
Atropine sulphate: Reverted the effects of ACTH-mediated activation of the vagus nerve [56]
Clorisondamine: Reverted the effects of high-fat diet-induced activation of vagus nerve [57]
Ischaemia/reperfusion VNS: Attenuated TNF in serum, heart and liver. Prevented the development of hypotension [55]
Myocardial ischaemia/reperfusion VNS: Decreased frequency of severe arrhythmias. Decreased free radical levels in blood. Ameliorated histopathological changes in the left ventricle and enhanced ERK1/2 activation. Reduced lethality [124] Atropine methylbromide: Abolished the effect of vagus nerve stimulation [124]
Renal ischaemia/reperfusion Nicotine and GTS-21: Improved renal function and decreased tubular necrosis and renal TNF [58].
Nicotine: Reduced renal TNF, KC and HMGB1. Improved renal function and reduced tubular damage [59]
Splanchnic artery occlusion shock VNS: Decreased NF-κB activity and prevented IκBα loss in the liver. Attenuated TNF mRNA in liver and serum TNF. Decreased leukocyte infiltration to the ileum and lung. Reverted hypotension and increased survival rate [54] Chlorisondamine: Reverted the effects of vagus nerve stimulation [54]
Inflammatory bowel disease Vagotomy: Increased disease activity index, macroscopic and histology scores, myeloperoxidase activity. Augmented IL-1β, IL-6 and TNF in colonic tissue [108] Nicotine reduced disease activity index in vagotomized rats but not in sham-operated rats. Hexamethonium (nicotinic antagonist) worsened disease activity index in sham-operated rats [108]
Others Nicotine, GTS and CAP55: Reduced TNF and IL-6 production by LPS-stimulated placenta cells. Possible role in preeclampsia [93]