Effect of α7n-Acetylcholine Receptor Activation and Antibodies to TNF-α on Mortality of Mice and Concentration of Proinflammatory Cytokines During Early Stage of Sepsis

Забродский, П. Ф.; Громов, М. С.; Maslyakov, V. V.

doi:10.1007/s10517-015-3063-x

Cited by 17 publications

(32 citation statements)

References 12 publications

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“…The vagus nerve system regulates the systemic and local inflammatory response4243, which is currently referred to as the cholinergic anti-inflammatory pathway. The anti-inflammatory effect of the vagus is mediated by acetylcholine, which interacting with α-7 submit nicotinic receptors located on macrophages and inhibit the cytokine production4445. For the past decade, the cholinergic anti-inflammatory pathway has been used to treat sepsis, inflammatory bowel and pancreatitis464748, and recently was introduced for POI treatment4950.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture treatment partly promotes the recovery time of postoperative ileus by activating the vagus nerve but not regulating local inflammation

Fang

Shao

et al. 2017

Sci Rep

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Postoperative ileus (POI) after abdominal surgery significantly lowers the life quality of patients and increase hospital costs. However, few treatment strategies have successfully shortened the duration of POI. Electroacupuncture (EA) is a modern way of administering acupuncture and widely used in various gastrointestinal (GI) diseases in the world. Here, we studied the effect of EA on POI and its underlying mechanisms. Intestinal manipulation resulted in significant delays of GI transit, colonic transit and gastric emptying. Surgery also up-regulated c-fos in nucleus of the solitary tract (NTS) and induced inflammation response in the small intestine. Further, operation and inhale anesthesia inhibited NTS neuron excitation duration for the whole observation time. EA administered at ST36 indeed shortened the recovery time of GI and colonic transit, and significantly increased the gastric emptying. EA also significantly activated the NTS neurons after operation. However, there was no anti-inflammation effect of EA during the whole experiment. Finally, atropine blocked the regulatory effect of EA on GI function, when it was injected after surgery, but not before surgery. Thus, the regulatory effect of EA on POI was mainly mediated by exciting NTS neurons to improve the GI tract transit function but not by activating cholinergic anti-inflammatory pathway.Abdominal and extra-abdominal surgery can lead to impaired motility of the entire gastrointestinal (GI) tract, which is referred to as postoperative ileus (POI) 1 . Depending on the type of surgery, POI may last over 2 weeks, with symptoms including nausea, vomiting, intolerance to food, absence of defecation, longer hospital stay 2 . Therefore, POI significantly increases the hospitalization costs.It is becoming increasingly clear that POI is associated with a localized inflammatory reaction, which is a complex orchestrated immune response to intestinal manipulation (IM) 1,3 . IM induced the influx of leukocytes, mainly monocytes, into the muscularis, after surgery [4][5][6] . Secretion of cytokines (IL-6, TNF-α ) from monocytes and smooth muscle inhibitory substances (NO, COX-2) contribute to the delay in intestinal transit 7,8 . These events delay GI transit, decrease local neuromuscular function and inhibit neurogenic pathways, thereby suppressing motility along the entire gastrointestinal tract for sustained postoperative periods 9,10

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Section: Discussionmentioning

confidence: 99%

Electroacupuncture treatment partly promotes the recovery time of postoperative ileus by activating the vagus nerve but not regulating local inflammation

Fang

Shao

et al. 2017

Sci Rep

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“…Moreover, an addictive beneficial effect of α7nAchR-agonists has been observed after the association with anti-TNF therapy during endotoxemia [65]. Therefore, the pharmacological α7nAchR activation of the cholinergic anti-inflammatory pathway characterizes an alternative approach to treating sepsis [66] and its importance has been supported by clinical studies.…”

Section: The Inflammatory Reflexmentioning

confidence: 99%

Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis

Kanashiro

Sônego

Ferreira

et al. 2017

Pharmacological Research

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Sepsis is one of the main causes of mortality in hospitalized patients. Despite the recent technical advances and the development of novel generation of antibiotics, severe sepsis remains a major clinical and scientific challenge in modern medicine. Unsuccessful efforts have been dedicated to the search of therapeutic options to treat the deleterious inflammatory components of sepsis. Recent findings on neuronal networks controlling immunity raised expectations for novel therapeutic strategies to promote the regulation of sterile inflammation, such as autoimmune diseases. Interesting studies have dissected the anatomical constituents of the so-called “cholinergic anti-inflammatory pathway”, suggesting that electrical vagus nerve stimulation and pharmacological activation of beta-2 adrenergic and alpha-7 nicotinic receptors could be alternative strategies for improving inflammatory conditions. However, the literature on infectious diseases, such as sepsis, is still controversial and, therefore, the real therapeutic potential of this neuroimmune pathway is not well defined. In this review, we will discuss the beneficial and detrimental effects of neural manipulation in sepsis, which depend on the multiple variables of the immune system and the nature of the infection. These observations suggest future critical studies to validate the clinical implications of vagal parasympathetic signaling in sepsis treatment.

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“…The second group of mice (control group 2, n=50) was injected subcutaneously once with saline (0.5ml), after 2 h mice received 2.5×10 9 CFUs in 2.0ml of saline diurnal culture of E. coli O157:H7 (sepsis modeling). 2,4,9,[16][17][18]20 Mice of the third group (n=40) were injected with OPC-DDVP (O, O-dimethyl-O-2,2-dichlorovinyl phosphate) (Sigma-Aldrich) intramuscularly once at a dose of 0.75 LD 50 in 0.5ml of a 0.25% solution of dimethyl sulfoxide (DMSO). DDVP was dissolved in DMSO, 0.25% aqueous solution containing a toxicant was prepared.…”

Section: Methodsmentioning

confidence: 99%

“…3,4 In the future, the study of the cholinergic anti-inflammatory pathway caused by the action of acetylcholine on α7n-acetylcholine receptors (α7nAChRs) cells of the monocyte-macrophage system (MMC), followed by inhibition of the production by the cells of proinflammatory cytokines (TNF-α, IL-1 β, IL-6) and reduced mortality from sepsis were devoted hundreds of articles various authors. 5,[9][10][11][12][13][14][15][16][17][18] Reduced production of TNF-α, IL-1β, IL-6 (anti-inflammatory effect occurrence) for cholinergic anti-inflammatory pathway is provided kinase JAK2, transcription factor STAT3, NF-κB transcription factor). 10,[16][17][18] The aim of the study was to evaluate the effect of acute intoxication of anticholinesterase compound in combination with its antidote cholinesterase reactivator carboxim on the mortality of mice from sepsis caused by experimental peritonitis (E. coli), and the concentration of pro-inflammatory cytokines TNFα, IL-1β and IL-6 in blood.…”

Section: Introductionmentioning

confidence: 99%

The combined effect of anticholinesterase compound DDVP and its antidote cholinesterase reactivator carboxim on implementation of cholinergic anti-inflammatory pathway

Забродский¹

2019

PPIJ

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Experiments on random-bred albino mice showed that the acute intoxication of anticholinesterase compounds (DDVP, 0.75 LD 50) is implemented the cholinergic antiinflammatory pathway (reduced mortality of mice from sepsis and the blood concentration of pro-inflammatory cytokines TNF-α, IL-1β, IL-6). Sepsis caused by the intraperitoneal administration of saline diurnal culture of E. coli O157:H7 (2.5×10 9 CFUs). The use of the cholinesterase reactivator carboxim (15mg/kg)-antidote of organophosphorus compounds-after acute intoxication of DDVP diminished affect the implementation of the cholinergic anti-inflammatory pathway.

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Effect of α7n-Acetylcholine Receptor Activation and Antibodies to TNF-α on Mortality of Mice and Concentration of Proinflammatory Cytokines During Early Stage of Sepsis

Cited by 17 publications

References 12 publications

Electroacupuncture treatment partly promotes the recovery time of postoperative ileus by activating the vagus nerve but not regulating local inflammation

Electroacupuncture treatment partly promotes the recovery time of postoperative ileus by activating the vagus nerve but not regulating local inflammation

Therapeutic potential and limitations of cholinergic anti-inflammatory pathway in sepsis

The combined effect of anticholinesterase compound DDVP and its antidote cholinesterase reactivator carboxim on implementation of cholinergic anti-inflammatory pathway

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