The contribution of the vagus nerve in interleukin-1β-induced fever is dependent on dose
Abstract
It has been suggested that proinflammatory cytokines communicate to the brain via a neural pathway involving activation of vagal afferents by interleukin-1β (IL-1β), in addition to blood-borne routes. In support, subdiaphragmatic vagotomy blocks IL-1β-induced, brain-mediated responses such as fever. However, vagotomy has also been reported to be ineffective. Neural signaling would be expected to be especially important at low doses of cytokine, when local actions could occur, but only very small quantities of cytokine would become systemic. Here, we examined core body temperature after intraperitoneal injections of three doses of recombinat human IL-1β (rh-IL-1β). Subdiaphragmatic vagotomy completely blocked the fever produced by 0.1 μg/kg, only partially blocked the fever produced by 0.5 μg/kg, and had no effect at all on the fever that followed 1.0 μg/kg rh-IL-1β. Blood levels of rh-IL-1β did not become greater than normal basal levels of endogenous rat IL-β until the 0.5-μg/kg dose nor was IL-1β induced in the pituitary until this dose. These results suggest that low doses of intraperitoneal IL-1β induce fever via a vagal route and that dose may account for some of the discrepancies in the literature.
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Sensory fibers traveling with the vagus nerve transmit information to the brain that is necessary and sufficient for initiating fever and other responses to injury or infection.
“sensory fibers traveling with the vagus nerve transmit information to the brain that is both necessary and sufficient for initiating fever and other responses to injury or infection (15,16).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [16]
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- Authors
- Hansen, M. K., O'Connor, K. A., Goehler, L. E., Watkins, L. R., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Department of Psychology and Center for Neuroscience, University of Colorado at Boulder, Boulder, Colorado 80309; and
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2001-04-01
- Volume
- 280
- Issue
- 4
- Pages
- R929-R934
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2188923454
- Cited by
- 169
- References
- 37
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 11 · 2020: 2 · 2019: 3 · 2018: 9 · 2017: 7 · 2016: 12 · 2015: 9 · 2014: 10 · 2013: 11 · 2012: 10
- FWCI
- 5.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01mh045045-12, 5r01mh055283-05)
- National Institute of Mental Health (MH-0155, MH55283, MH-00314, MH-45045)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Keywords
- vagus nerve, IL-1β, fever, vagotomy, vagal afferents, neuroimmune interactions, core body temperature, pituitary gland, systemic cytokine response
- MeSH terms
- Animals, Body Temperature, Body Temperature Regulation, Brain, Diaphragm, Dose-Response Relationship, Drug, Fever, Humans, Interleukin-1, Male, Muscle Denervation, Recombinant Proteins, Vagotomy, Vagus Nerve, Rats, Sprague-Dawley, Rats
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