Central activation of the cholinergic anti‐inflammatory pathway reduces surgical inflammation in experimental post‐operative ileus

The, FO; Cailotto, Cathy; Vliet, Jan van der; Jonge, WJ de; Bennink, R.J.; Buijs, R.M.; Boeckxstaens, G. E.

doi:10.1111/j.1476-5381.2011.01296.x

“…Therefore, mast cell inhibition as a bona fide drug target could be one of the future treatment concepts to prevent POI [45]. In an experimental study, electric stimulation of the vagus nerve and central activation of anti-inflammatory cholinergic pathways by intravenous semapimod (an inhibitor of p38 mitogen-activated protein kinase) reduced tissue inflammation and the appearance of POI [47]. …”

Section: Resultsmentioning

confidence: 99%

Fast-Track Surgery – Conditions and Challenges in Postsurgical Treatment: A Review of Elements of Translational Research in Enhanced Recovery after Surgery

Hoffmann¹,

Kettelhack²

2012

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Background: Enhanced recovery after surgery (ERAS) or fast-track surgery is a perioperative and postoperative care concept initiated in the early 1990s aiming to reduce the length of hospital stays following elective abdominal surgery. Twenty treatment items defined in the Consensus Guidelines established in 2009 were included in this concept. The success of ERAS depends highly on multidisciplinary teamwork and patient compliance. Several ERAS items and their impact on perioperative and postoperative care have recently been discussed. In this connection, translational research topics triggered increasing interest in ERAS and new impulses aimed at improving the ERAS concept. We thus reviewed the surgical literature to highlight the role of translational research items in ERAS. Methods: A literature search of Medline®, PubMed® and the Cochrane Database was performed. Two investigators independently reviewed the abstracts and appropriate articles were included in this review. Results: Articles have been selected. The advantages of the ERAS concept over conventional postoperative care were established by four meta-analyses and several reviews. But, due to the lack of standardization of the protocols, the level of evidence is still low. The implementation of ERAS into clinical practice is furthermore hampered by the poor compliance with ERAS protocols and remains a challenge for the future. Moreover, recent trials challenge the role of some ERAS items, e.g. epidural anesthesia. Translational research trials investigating stress, immune and inflammatory response after surgery, new analgesic concepts, goal-directed fluid therapy and new drugs and substances to improve the outcome of ERAS provide first promising data but still need to be integrated in the ERAS concept. Conclusion: The Consensus Guidelines for ERAS are subject to the constant evolution of treatment strategies and implementation of translational research findings. Improvement of the compliance with ERAS protocols in surgical clinics and updating of ERAS items taking into account recent findings in translational research may improve the outcomes of ERAS but remain a long-term challenge in surgery for the next years.

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“…83 VN stimulation via electrical current,51 high-fat enteral feeding84 or central application of semapimod,85 as well as peripheral α7nAChR activation via AR-R1777983 all resulted in reduction of influx of immune cells into the muscularis, dampened cytokine production and improved gastrointestinal transit. In line with the findings reported in sepsis,13 the anti-inflammatory effect of electrical VN stimulation is lost in α7nAChR-deficient mice,53 confirming the involvement of α7nAChR also in the gut.…”

Section: Postoperative and Endotoxin-induced Ileusmentioning

confidence: 99%

The vagal innervation of the gut and immune homeostasis

Matteoli

¹

,

Boeckxstaens

²

2012

Gut

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The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

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“…46 Several lines of preclinical evidence indicate that activation of the cholinergic anti-inflammatory pathway may be an efficient strategy to prevent POI ( figure 3). 83 VN stimulation via electrical current, 51 high-fat enteral feeding 84 or central application of semapimod, 85 as well as peripheral α7nAChR activation via AR-R17779 83 all resulted in reduction of influx of immune cells into the muscularis, dampened cytokine production and improved gastrointestinal transit. In line with the findings reported in sepsis, 13 the anti-inflammatory effect of electrical VN stimulation is lost in α7nAChR-deficient mice, 53 confirming the involvement of α7nAChR also in the gut.…”

Section: Postoperative and Endotoxin-induced Ileusmentioning

confidence: 99%

The vagal innervation of the gut and immune homeostasis

Matteoli

¹

,

Gomez‐Pinilla

²

,

Giovangiulio

³

et al. 2015

Autonomic Neuroscience

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The central nervous system interacts dynamically with the immune system to modulate inflammation through humoral and neural pathways. Recently, in animal models of sepsis, the vagus nerve (VN) has been proposed to play a crucial role in the regulation of the immune response, also referred to as the cholinergic anti-inflammatory pathway. The VN, through release of acetylcholine, dampens immune cell activation by interacting with α-7 nicotinic acetylcholine receptors. Recent evidence suggests that the vagal innervation of the gastrointestinal tract also plays a major role controlling intestinal immune activation. Indeed, VN electrical stimulation potently reduces intestinal inflammation restoring intestinal homeostasis, whereas vagotomy has the reverse effect. In this review, we will discuss the current understanding concerning the mechanisms and effects involved in the cholinergic anti-inflammatory pathway in the gastrointestinal tract. Deeper investigation on this counter-regulatory neuroimmune mechanism will provide new insights in the cross-talk between the nervous and immune system leading to the identification of new therapeutic targets to treat intestinal immune disease.

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Central activation of the cholinergic anti‐inflammatory pathway reduces surgical inflammation in experimental post‐operative ileus

Abstract: Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve.

Cited by 85 publications

References 38 publications

Fast-Track Surgery – Conditions and Challenges in Postsurgical Treatment: A Review of Elements of Translational Research in Enhanced Recovery after Surgery

Fast-Track Surgery – Conditions and Challenges in Postsurgical Treatment: A Review of Elements of Translational Research in Enhanced Recovery after Surgery

The vagal innervation of the gut and immune homeostasis

The vagal innervation of the gut and immune homeostasis

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