scholarly journals Vagal-Immune Interactions Involved in Cholinergic Anti-Inflammatory Pathway

2017 ◽  
pp. S139-S145 ◽  
Author(s):  
I. ZILA ◽  
D. MOKRA ◽  
J. KOPINCOVA ◽  
M. KOLOMAZNIK ◽  
M. JAVORKA ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Vagus Nerve ◽  
Current Knowledge ◽  
Nervous Activity ◽  
Treatment Strategies ◽  
Therapeutic Effects ◽  
Vagal Activity ◽  
Inflammatory Pathway ◽  
Autonomic Nervous ◽  
Anti Inflammatory

Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacolo-gical/electrical modulation of vagal activity suppressed TNF-α and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

scholarly journals Electroacupuncture Ameliorates Acute Pancreatitis: A Role for the Vagus Nerve–Mediated Cholinergic Anti-Inflammatory Pathway

2021 ◽  
Vol 8 ◽  
Author(s):  
Luyao Zhang ◽  
Zhiyang Wu ◽  
Jing Zhou ◽  
Shengfeng Lu ◽  
Chaofan Wang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Nervous System ◽  
Autonomic Nervous System ◽  
Vagus Nerve ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Inflammatory Pathway ◽  
Autonomic Nervous ◽  
Duct Ligation ◽  
Anti Inflammatory

Organ failure resulting from excessive inflammation is the leading cause of death in the early phase of acute pancreatitis (AP). The autonomic nervous system was reported to be involved in AP, and the vagus nerve could exert anti-inflammatory effects through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. Acupuncture has been widely used in traditional Asian medicine, and recent studies suggested the inflammation modulating effect of electroacupuncture (EA) might be mediated by the autonomic nervous system. In this study, we aimed to investigate the effects of EA in AP animal models. Two independent AP mouse models were used, namely, caerulein hyperstimulation and pancreatic duct ligation. We found that EA at Zusanli acupoint increased vagus nerve activity, suppressed systemic inflammation, and alleviated the histopathological manifestations and leukocyte infiltrations of the pancreas. Induction of AP resulted in a remarkable decrease in the frequency of α7nAchR+ macrophages in the pancreas, while EA counteracted this phenomenon. The anti-inflammatory, pancreatic protective and upregulation of α7nAchR effects of EA were reduced in mice with vagotomy. Moreover, the therapeutic effects of EA were attenuated in mice treated with methyllycaconitine citrate, a selective α7nAChR antagonist. Taken together, EA could modulate inflammation, thereby exerting protective effects in AP. The mechanism may include activating the vagus nerve through the cholinergic anti-inflammatory pathway.

Controlling inflammation: the cholinergic anti-inflammatory pathway

2006 ◽  
Vol 34 (6) ◽  
pp. 1037-1040 ◽  
Author(s):  
V.A. Pavlov ◽  
K.J. Tracey
Keyword(s):  
Vagus Nerve ◽  
Nicotinic Receptor ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Experimental Models ◽  
Innate Immune Responses ◽  
Receptor Ligands ◽  
Inflammatory Pathway ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

Innate immune responses and inflammation are regulated in part by neural mechanisms. In the present paper, we summarize experimental evidence that reveals that innate immunity and inflammation are controlled by the vagus nerve, previously known as a regulator of other vital physiological functions. Activation of vagus nerve cholinergic signalling inhibits TNF (tumour necrosis factor) and other pro-inflammatory cytokine overproduction through ‘immune’ α7 nicotinic receptor-mediated mechanisms. This efferent vagus nerve-based ‘cholinergic anti-inflammatory pathway’ has been elucidated as a critical regulator of inflammation in several experimental models of diseases. Our recent observations have shown that activation of central (brain) cholinergic transmission by selective muscarinic receptor ligands results in lower systemic TNF levels in rodents and indicate that the efferent vagus nerve may provide a functional brain-to-immune connection. Thus central cholinergic signalling is implicated in the activation of the cholinergic anti-inflammatory pathway. Electrical vagus nerve stimulation is clinically approved for the treatment of epilepsy and depression and current knowledge suggests that it could be utilized to control inflammation. Advances in understanding the receptor and molecular mechanisms of cholinergic anti-inflammatory signalling indicate that selective α7 nicotinic receptor agonists and centrally acting cholinergic enhancers can be used in the treatment of pathological conditions characterized by cytokine overproduction.

scholarly journals The Cholinergic Anti-Inflammatory Pathway as a Conceptual Framework to Treat Inflammation-Mediated Renal Injury

2019 ◽  
Vol 44 (4) ◽  
pp. 435-448 ◽  
Author(s):  
Jonas Jarczyk ◽  
Benito A. Yard ◽  
Simone Hoeger
Keyword(s):  
Vagus Nerve ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Kidney Injury ◽  
Organ Injury ◽  
Inflammatory Pathway ◽  
Inflammatory Conditions ◽  
Promising Strategy ◽  
Anti Inflammatory ◽  
The Brain

Background: The cholinergic anti-inflammatory pathway, positioned at the interface of the nervous and immune systems, is the efferent limb of the “inflammatory reflex” which mainly signals through the vagus nerve. As such, the brain can modulate peripheral inflammatory responses by the activation of vagal efferent fibers. Importantly, immune cells in the spleen express most cholinergic system components such as acetylcholine (ACh), choline acetyltransferase, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors, making communication between both systems possible. In general, this communication down-regulates the inflammation, achieved through different mechanisms and depending on the cells involved. Summary: With the awareness that the cholinergic anti-inflammatory pathway serves to prevent or limit inflammation in peripheral organs, vagus nerve stimulation has become a promising strategy in the treatment of several inflammatory conditions. Both pharmacological and non-pharmacological methods have been used in many studies to limit organ injury as a consequence of inflammation. Key Messages: In this review, we will highlight our current knowledge of the cholinergic anti-inflammatory pathway, with emphasis on its potential clinical use in the treatment of inflammation-triggered kidney injury.

Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway

2013 ◽  
Vol 25 (3) ◽  
pp. 208-221 ◽  
Author(s):  
B. Bonaz ◽  
C. Picq ◽  
V. Sinniger ◽  
J. F. Mayol ◽  
D. Clarençon
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Inflammatory Pathway ◽  
Anti Inflammatory

Intracerebral Hemorrhage, Vagus Nerve Stimulation, and Anti-Inflammatory Response

2016 ◽  
Vol 93 ◽  
pp. 423-424 ◽  
Author(s):  
Leonardo C. Welling ◽  
Mariana S. Welling ◽  
Manoel Jacobsen Teixeira ◽  
Eberval Gadelha Figueiredo
Keyword(s):  
Inflammatory Response ◽  
Intracerebral Hemorrhage ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Anti Inflammatory

129 Stimulating the Cholinergic Anti-inflammatory Pathway Alters Inflammatory Cell Mobilization after Burn Injury

2021 ◽  
Vol 42 (Supplement_1) ◽  
pp. S87-S87
Author(s):  
Todd Costantini ◽  
Jessica Weaver ◽  
Brian Eliceiri
Keyword(s):  
Bone Marrow ◽  
Vagus Nerve ◽  
Burn Injury ◽  
Myeloid Cell ◽  
Inflammatory Cells ◽  
Severe Burn ◽  
Inflammatory Pathway ◽  
Anti Inflammatory ◽  
Severe Burn Injury ◽  
Patrolling Monocytes

Abstract Introduction Severe burn injury causes a systemic inflammatory response (SIRS) that is characterized by mobilization of inflammatory cells into the circulation and is associated with distant organ injury that can lead to significant morbidity and mortality. The cholinergic anti-inflammatory pathway, mediated by the vagus nerve, regulates the anti-inflammatory response to injury and infection. We have previously shown in models of burn injury that stimulating the vagus nerve may be a potential therapy aimed at limiting SIRS. Here, we hypothesized that stimulating the vagus nerve (VNS) would limit the SIRS response by altering the mobilization and trafficking of inflammatory cells after burn injury. Methods Wild type 10–12-week-old C57BL/6 mice were injured with a 30% total body surface area steam burn. A separate cohort of animals was treated with electrical stimulation of the cervical vagus nerve for 10 minutes immediately post-burn. Bone marrow, blood and lung tissue were collected 24 hours after burn injury. Flow cytometry of bone marrow was performed to measure Lineage- c-kit± Sca-1+ (LSK) hematopoietic stem cells (HSC), then further analyzed to quantify changes in Long-term (LT) HSC, short-term (ST) HSC, and Multipotential Progenitor (MPP) compartments. Bone marrow, blood and perfused lung tissue were analyzed by flow cytometry using a panel of myeloid cell markers. Results Severe burn injury decreased bone marrow LSK expression by 50% compared to sham, with LT-HSC and MPP expression decreasing to a greater degree than ST-HSCs. VNS did not alter burn-induced changes in any bone marrow HSC cell type. Burn injury was associated with increased mobilization of CD45+CD11b+ monocytes and CD11b+Ly6Chi inflammatory monocytes into the peripheral blood and lung, while increased CD11b+Ly6Clo patrolling monocytes and Gr1+Ly6C- neutrophils was seen in the lung only. VNS significantly prevented the burn-induced increase in CD45+ inflammatory cells, CD11b+Ly6Clo patrolling monocytes and Gr1+Ly6C- neutrophils in the lung (see Figure), reducing their expression to sham levels, despite only modest changes to myeloid cell expression in the blood. Conclusions VNS attenuates myeloid cell cell trafficking to the lung after severe burn injury despite having no effect on emergency myelopoiesis in the bone marrow. Further studies are needed to define the mechanism by which the cholinergic anti-inflammatory pathway attenuates the SIRS response to burn.

scholarly journals The cholinergic anti-inflammatory pathway in chronic kidney disease—review and vagus nerve stimulation clinical pilot study

2020 ◽  
Vol 35 (11) ◽  
pp. 1840-1852
Author(s):  
Marie Hilderman ◽  
Annette Bruchfeld
Keyword(s):  
Chronic Kidney Disease ◽  
Pilot Study ◽  
Kidney Disease ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Cell Injury ◽  
Inflammatory Pathway ◽  
Increased Risk ◽  
Anti Inflammatory

Abstract Inflammation and autonomic dysfunction are common findings in chronic and end-stage kidney disease and contribute to a markedly increased risk of mortality in this patient population. The cholinergic anti-inflammatory pathway (CAP) is a vagal neuro-immune circuit that upholds the homoeostatic balance of inflammatory activity in response to cell injury and pathogens. CAP models have been examined in preclinical studies to investigate its significance in a range of clinical inflammatory conditions and diseases. More recently, cervical vagus nerve stimulation (VNS) implants have been shown to be of potential benefit for patients with chronic autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease. We have previously shown that dialysis patients have a functional CAP ex vivo. Here we review the field and the potential role of the CAP in acute kidney injury and chronic kidney disease (CKD) as well as in hypertension. We also present a VNS pilot study in haemodialysis patients. Controlling inflammation by neuroimmune modulation may lead to new therapeutic modalities for improved treatment, outcome, prognosis and quality of life for patients with CKD.

The effects of aging, injury and disease on microglial function: a case for cellular senescence

2007 ◽  
Vol 3 (3) ◽  
pp. 245-253 ◽  
Author(s):  
Kelly R. Miller ◽  
Wolfgang J. Streit
Keyword(s):  
Neurodegenerative Diseases ◽  
Cellular Senescence ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Aging Brain ◽  
Normal Brain ◽  
Age Related ◽  
Anti Inflammatory ◽  
Effects Of Aging ◽  
And Function

AbstractNeuroinflammation resulting from chronic reactive microgliosis is thought to contribute to age-related neurodegeneration, as well as age-related neurodegenerative diseases, specifically Alzheimer's disease (AD). Support of this theory comes from studies reporting a progressive, age-associated increase in microglia with an activated phenotype. Although the underlying cause(s) of this microglial reactivity is idiopathic, an accepted therapeutic strategy for the treatment of AD is inhibition of microglial activation using anti-inflammatory agents. Although the effectiveness of anti-inflammatory treatment for AD remains equivocal, microglial inhibition is being tested as a potential treatment for additional neurodegenerative disorders including amyotrophic lateral sclerosis and Parkinson's disease. Given the important and necessary functions of microglia in normal brain, careful evaluation of microglial function in the aged brain is a necessary first step in targeting more precise treatment strategies for aging-related neurodegenerative diseases. Studies from our laboratory have shown multiple age-related changes in microglial morphology and function that are suggestive of cellular senescence. In this manuscript, we review current knowledge of microglia in the aging brain and present new, unpublished work that further supports the theory that microglia experience an age-related decline in proliferative function as a result of cellular senescence.

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