The vagus nerve and nicotinic receptors modulate experimental pancreatitis severity in mice

Author(s): van Westerloo DJ, Giebelen IA, Florquin S, Bruno MJ, Larosa GJ, et al.


Background & aims:The nervous system, through the vagus nerve, controls inflammation by decreasing the release of tumor necrosis factor-alpha from endotoxin stimulated macrophages. This anti-inflammatory effect is mediated by an interaction of acetylcholine, the principal neurotransmitter of the vagus nerve, with macrophage cholinergic nicotinic receptors expressing the alpha7 subunit.

Methods:To determine the role of this "nicotinic anti-inflammatory pathway" in experimental pancreatitis, we induced pancreatitis in mice by 12 hourly intraperitoneal injections of cerulein. Pancreatitis was preceded by unilateral left cervical vagotomy or pretreatment with the nicotinic receptor antagonist mecamylamine or by pretreatment with the selective alpha7 nicotinic receptor agonist 3-(2,4-dimethoxybenzylidene) anabaseine (GTS-21).

Results:Vagotomy or pretreatment with mecamylamine resulted in an enhanced severity of pancreatitis, as reflected by histology, edema, plasma hydrolases, and interleukin-6 levels. Furthermore, the number of neutrophils migrated to the pancreas was increased in these mice, as shown by myeloperoxidase content and intrapancreatic staining of neutrophils. Conversely, GTS-21 pretreatment strongly decreased the severity of pancreatitis. Pancreatitis-associated pulmonary inflammation was independent of the integrity of the vagus nerve and nicotinic receptors.

Conclusions:This study provides the first evidence for a therapeutic potential of the vagus nerve and the "nicotinic anti-inflammatory pathway" in attenuating inflammation and injury during experimental pancreatitis.

Similar Articles

Pathophysiology and management of bowel dysfunction in multiple sclerosis

Author(s): Wiesel PH, Norton C, Glickman S, Kamm MA

Fatigue in MS is related to sympathetic vasomotor dysfunction

Author(s): Flachenecker P, Rufer A, Bihler I, Hippel C, Reiners K, et al.

"Is Fatigue in Patients with Multiple Sclerosis Related to Autonomic Dysfunction?" Clin Auto Res 10: 169-175

Author(s): Keselbrener L, Akselrod S, Ahiron A, Eldar M, Barak Y, et al.

"Clinical Screening of Autonomic Dysfunction in Multiple Sclerosis

Author(s): Hale LA, Nukada H, Du Plessis LJ, Peebles KC

Reflex control of immunity

Author(s): Tracey KJ

Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis

Author(s): Birnbaum G, Cree B, Altafullah I, Zinser M, Reder AT

Inhibitory role for GABA in autoimmune inflammation

Author(s): Bhat R, Axtell R, Mitra A, Miranda M, Lock C, et al.

Effects of sedatives on noradrenaline release from the medial prefrontal cortex in rats

Author(s): Kubota T, Hirota K, Yoshida H, Takahashi S, Anzawa N, et al.

Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin

Author(s): Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, et al.

Local stimulation of alpha7 cholinergic receptors inhibits LPS-induced TNF-alpha release in the mouse lung

Author(s): Giebelen IA, van Westerloo DJ, LaRosa GJ, de Vos AF, van der Poll T

Physiologic and functional responses of MS patients to body cooling

Author(s): Ku YT, Montgomery LD, Lee HC, Luna B, Webbon BW