ArticleProceedings of the National Academy of Sciences of the United States of America2006
Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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Who cites it
147 citing papers in PubMed, 330 citations in OpenAlex.
- The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial.Frontiers in immunology · 2021Trial
- Cervical sympathetic block regulates early systemic inflammatory response in severe trauma patients.Medical science monitor : international medical journal of experimental and clinical research · 2013Trial
- Vagus nerve as the hub in peripheral immune-inflammatory response: implications for related therapeutic drugs.Molecular biology reports · 2026Review
- A Review of Vagus Nerve Stimulation for Disease: Comprehensive Theory and Evidence for Mechanisms of Action.Comprehensive physiology · 2026Review
- The roles of the nerve-immune axis in modulating bone regeneration.Bone research · 2026Review
- Sympathetic regulation of bone homeostasis and remodeling: molecular mechanisms, pathophysiological roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction.Journal of the American Society of Nephrology : JASN · 2025Review
- Loss of M1 Acetylcholine Receptor-mediated Orexinergic Activity Contributes to Immune Dysfunction in Experimental Sepsis.Research square · 2025Article
- Water-Soluble Ginseng Oligosaccharides Prevent Scopolamine-Induced Cholinergic Dysfunction and Inflammatory Cytokine Overexpression.Cell biochemistry and biophysics · 2025Article
- Associations between functional autoantibodies targeting GPCRs, antinuclear antibodies, and inflammatory cytokines TNF-α: a cross-sectional study of 19,810 individuals.Frontiers in immunology · 2025Article
- Analysis of the association between cholinesterase and in-hospital mortality in children with bloodstream infections in the pediatric intensive care unit.Frontiers in pediatrics · 2025Article
- Novel opportunities for treating complex neuropsychiatric and neurocognitive conditions based on recent developments with xanomeline.Frontiers in psychiatry · 2025Article
- Relevance of Saliva Analyses in Terms of Etiological Factors, Biomarkers, and Indicators of Disease Course in Patients with Multiple Sclerosis-A Review.International journal of molecular sciences · 2024Review
- Nicotinic and Muscarinic Acetylcholine Receptor Agonists Counteract Cognitive Impairment in a Rat Model of Doxorubicin-Induced Chemobrain via Attenuation of Multiple Programmed Cell Death Pathways.Molecular neurobiology · 2024Article
- Electrical stimulation of the dorsal motor nucleus of the vagus in male mice can regulate inflammation without affecting the heart rate.Brain, behavior, and immunity · 2024Article
- Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden.Nature reviews. Cardiology · 2024Review
- Bridging cholinergic signalling and inflammation in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2024Article
- Alpha 7 nicotinic acetylcholine receptors signaling boosts cell-cell interactions in macrophages effecting anti-inflammatory and organ protection.Communications biology · 2023Article
- Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.Behavioral and brain functions : BBF · 2023Article
- Saliva and Serum Acetylcholinesterase Activity in Multiple Sclerosis.Molecular neurobiology · 2023Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
TNF has a critical mediator role in inflammation and is an important therapeutic target. We recently discovered that TNF production is regulated by neural signals through the vagus nerve. Activation of this "cholinergic antiinflammatory pathway" inhibits the production of TNF and other cytokines and protects animals from the inflammatory damage caused by endotoxemia and severe sepsis. Here, we describe a role for central muscarinic acetylcholine receptors in the activation of the cholinergic antiinflammatory pathway. Central muscarinic cholinergic activation by muscarine, the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF levels significantly during endotoxemia. Centrally administered methoctramine stimulated vagus-nerve activity measured by changes in instantaneous heart-rate variability. Blockade of peripheral muscarinic receptors did not abolish antiinflammatory signaling through the vagus nerve, indicating that peripheral muscarinic receptors on immune cells are not required for the cytokine-regulating activities of the cholinergic antiinflammatory pathway. The role of central muscarinic receptors in activating the cholinergic antiinflammatory pathway is of interest for the use of centrally acting muscarinic cholinergic enhancers as antiinflammatory agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.