ArticleThe Journal of physiology2014
Reflex control of inflammation by sympathetic nerves, not the vagus.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
118 citing papers in PubMed, 237 citations in OpenAlex.
- Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial.European heart journal · 2015Trial
- Transcutaneous auricular vagus nerve stimulation for anxiety symptoms across fear, trauma, and disease contexts: a narrative review of clinical evidence and mechanisms.European archives of psychiatry and clinical neuroscience · 2026Review
- Endotoxin-induced inflammation promotes, via the adrenomedullary system, a hyperglycemic and anti-inflammatory reflex.Brain, behavior, & immunity - health · 2026Article
- Peripheral catecholamine systems: an evolutionary perspective.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Review
- Neuro-immune regulation of sepsis-associated delirium via the PBN-CeA-spleen axis.Journal of neuroinflammation · 2025Article
- The sympathetic nervous system enhances host immune responses to enteric bacterial pathogens in mice.Brain, behavior, and immunity · 2025Article
- Molecular and functional diversity of the autonomic nervous system.Nature reviews. Neuroscience · 2025Review
- From thought to action: The organization of spinal projecting neurons.Cell reports · 2025Review
- Beta Adrenergic Signaling as a Therapeutic Target for Autoimmunity.bioRxiv : the preprint server for biology · 2025Article
- Transcutaneous auricular vagus nerve stimulation inhibits mental stress-induced cortisol release-Potential implications for inflammatory conditions.Physiological reports · 2025Article
- The molecular components of the anti-inflammatory cholinergic pathway are extrasplenic.PloS one · 2025Article
- The bidirectional regulatory mechanism of gut microbiota metabolites on myocardial injury in heart failure from the perspective of the gut-heart axis: a review.Frontiers in microbiology · 2025Review
- Acupuncture at Zusanli (ST36) for the benefits of sepsis-laboratory evidence for "preventive treatment of disease" and "holistic concept" in the protective effects of acupuncture: a literature review of rodent studies.Frontiers in neurology · 2025Review
- Catecholamines Attenuate LPS-Induced Inflammation through β2 Adrenergic Receptor Activation- and PKA Phosphorylation-Mediated TLR4 Downregulation in Macrophages.Current issues in molecular biology · 2024Article
- Characterization of idiopathic chronic diarrhea and associated intestinal inflammation and preliminary observations of effects of vagal nerve stimulation in a non-human primate.Neurogastroenterology and motility · 2024Article
- Non-invasive ventral cervical magnetoneurography as a proxy of in vivo lipopolysaccharide-induced inflammation.Communications biology · 2024Article
- Targeting S100A9 Prevents β-Adrenergic Activation-Induced Cardiac Injury.Inflammation · 2024Article
- The immunomodulatory effect of oral NaHCOJournal of neuroinflammation · 2024Article
- Molecular cell types as functional units of the efferent vagus nerve.Seminars in cell & developmental biology · 2024Review
- Transcutaneous vagus nerve stimulation: a bibliometric study on current research hotspots and status.Frontiers in neuroscience · 2024Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We investigated a neural reflex that controls the strength of inflammatory responses to immune challenge - the inflammatory reflex. In anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 60 μg kg(-1)), we found strong increases in plasma levels of the key inflammatory mediator tumour necrosis factor α (TNFα) 90 min later. Those levels were unaffected by previous bilateral cervical vagotomy, but were enhanced approximately 5-fold if the greater splanchnic sympathetic nerves had been cut. Sham surgery had no effect, and plasma corticosterone levels were unaffected by nerve sections, so could not explain this result. Electrophysiological recordings demonstrated that efferent neural activity in the splanchnic nerve and its splenic branch was strongly increased by LPS treatment. Splenic nerve activity was dependent on inputs from the splanchnic nerves: vagotomy had no effect on the activity in either nerve. Together, these data demonstrate that immune challenge with this dose of LPS activates a neural reflex that is powerful enough to cause an 80% suppression of the acute systemic inflammatory response. The efferent arm of this reflex is in the splanchnic sympathetic nerves, not the vagi as previously proposed. As with other physiological responses to immune challenge, the afferent pathway is presumptively humoral: the present data show that vagal afferents play no measurable part. Because inflammation sits at the gateway to immune responses, this reflex could play an important role in immune function as well as inflammatory diseases.
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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.