ArticleMolecular medicine (Cambridge, Mass.)2023
Transient Receptor Potential Ankyrin-1-expressing vagus nerve fibers mediate IL-1β induced hypothermia and reflex anti-inflammatory responses.
Article in Molecular medicine (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 24 citations in OpenAlex.
- Hypothalamic regulation of sepsis-associated anorexia: cytokine and hormonal signalling through AgRP/POMC circuits.EMBO molecular medicine · 2026Review
- Central neurons encode interleukin-1β signals and mediate stress-induced inflammation.The Journal of experimental medicine · 2026Article
- IL-1β engages distinct peripheral sensory circuits to suppress feeding across time.bioRxiv : the preprint server for biology · 2026Article
- Colitis-associated gut-vagus-brain signaling integrates tumorigenesis and neuroinflammation: comparative regulation by vagotomy and atropine.Journal of neuroinflammation · 2026Article
- Long-term dietary allyl isothiocyanate, a TRPA1 agonist, ameliorates cardiac fibrosis and diastolic dysfunction in aged mice.GeroScience · 2025Article
- Neural representation of cytokines by vagal sensory neurons.Nature communications · 2025Article
- Ion Currents Mediated by TRPA1 Channels in Freshly Dissociated Rat Articular Chondrocytes: Biophysical Properties and Regulation by Inflammatory Processes.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Role of macrophages in neuroimmune regulation.Frontiers in immunology · 2025Review
- The Modulation of Neuroimmune Responses in Peripheral Inflammation.Journal of inflammation research · 2025Review
- Lipopolysaccharide-mediated effects of the microbiota on sleep and body temperature.Scientific reports · 2024Article
- Cytokines reprogram airway sensory neurons in asthma.bioRxiv : the preprint server for biology · 2024Article
- The Role of TRP Channels in Sepsis and Colitis.International journal of molecular sciences · 2024Review
- Unveiling the role of TRPA1 in cardiovascular health and disease: a mini review.Frontiers in cardiovascular medicine · 2024Review
- ZO-1 and IL-1RAP Phosphorylation: Potential Role in Mediated Brain-Gut Axis Dysregulation in Irritable Bowel Syndrome-like Stressed Mice.International journal of medical sciences · 2024Article
- The Fifth Bioelectronic Medicine Summit: today's tools, tomorrow's therapies.Bioelectronic medicine · 2023Article
- The Effect of Postinduction Blood Glucose on Intraoperative Hypothermia.Medicina (Kaunas, Lithuania) · 2023Observational
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16 authors at 1 institution in 1 country.
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Abstract
backgroundInflammation, the physiological response to infection and injury, is coordinated by the immune and nervous systems. Interleukin-1β (IL-1β) and other cytokines produced during inflammatory responses activate sensory neurons (nociceptors) to mediate the onset of pain, sickness behavior, and metabolic responses. Although nociceptors expressing Transient Receptor Potential Ankyrin-1 (TRPA1) can initiate inflammation, comparatively little is known about the role of TRPA1 nociceptors in the physiological responses to specific cytokines.
methodsTo monitor body temperature in conscious and unrestrained mice, telemetry probes were implanted into peritoneal cavity of mice. Using transgenic and tissue specific knockouts and chemogenetic techniques, we recorded temperature responses to the potent pro-inflammatory cytokine IL-1β. Using calcium imaging, whole cell patch clamping and whole nerve recordings, we investigated the role of TRPA1 during IL-1β-mediated neuronal activation. Mouse models of acute endotoxemia and sepsis were used to elucidate how specific activation, with optogenetics and chemogenetics, or ablation of TRPA1 neurons can affect the outcomes of inflammatory insults. All statistical tests were performed with GraphPad Prism 9 software and for all analyses, P ≤ 0.05 was considered statistically significant.
resultsHere, we describe a previously unrecognized mechanism by which IL-1β activates afferent vagus nerve fibers to trigger hypothermia, a response which is abolished by selective silencing of neuronal TRPA1. Afferent vagus nerve TRPA1 signaling also inhibits endotoxin-stimulated cytokine storm and significantly reduces the lethality of bacterial sepsis.
conclusionThus, IL-1β activates TRPA1 vagus nerve signaling in the afferent arm of a reflex anti-inflammatory response which inhibits cytokine release, induces hypothermia, and reduces the mortality of infection. This discovery establishes that TRPA1, an ion channel known previously as a pro-inflammatory detector of cold, pain, itch, and a wide variety of noxious molecules, also plays a specific anti-inflammatory role via activating reflex anti-inflammatory activity.
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