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Vagotomy attenuates behavioural effects of interleukin-1 injected peripherally but not centrally
Abstract
Peripheral and central injections of recombinant rat interleukin-1 beta (IL-1 beta) have been shown to decrease social exploration in rats. To test the involvement of vagal afferents in the communication between the immune system and the brain, sham-operated and vagotomized rats were injected peripherally or centrally with physiological saline or IL-1 beta 4 weeks after surgery. Vagotomy attenuated the depression in social exploration induced by i.p. administration of IL-1 beta (15 micrograms) but did not alter the behaviour-depressing effects of an intracerebroventricular (i.c.v.) injection of IL-1 beta (45 ng). These results confirm the role of vagal afferent nerves in the transmission of an immune message from the periphery to the brain, and show that vagotomy does not impair the direct sensitivity of the brain itself to immune signals.
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“Preclinical studies of neural communication between the CNS and the peripheral immune system have targeted the vagus nerve, and demonstrate that vagotomy (sub-diaphragmatic transection of the vagus nerve) blocks or alters the dynamics of peripheral immune system communication to the CNS”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Bluthe et al, 1996
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“injection of IL-1b cannot exert its central actions after vagotomy (7).”
BackgroundRyan, K. M., Griffin, É. W., Ryan, K. J., Tanveer, R., Vanattou‐Saïfoudine, N., McNamee, E. N., Fallon, E., Heffernan, S., Harkin, A., & Connor, T. J. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.02.023 · Cited by 11
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“, 1992) and the usual hormonal and nutritional outputs of digestive processes, but also by “visceral error signals,” namely the ones associated with local and generalized inflammation (Juhasz et al., 1985; Bluthé et al., 1996; Simons et al., 1998; Hosoi et al., 2000; Bazar et al., 2004; Burdakov and Alexopoulos, 2005;…”
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“However, it should be underlined, although some controversies still exist, that generally they are both considered reliable markers (Bluthe et al. 1996; Marazziti et al. 2012).”
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“This has been functionally demonstrated by vagal nerve resection experiments that abrogated LPS-induced inflammation and sickness behavior in rodents [140,141].”
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Self-citationJung, E. Y., Kim, K. S., & Shim, I. (2008) · Experimental Neurobiology · doi:10.5607/en.2008.17.2.47
“…peripherally or into the CNS, produces fever (Kluger, 1991) reduced food and water intake (PlataSalaman et al., 1998), reduced social interaction (Bluthe et al., 1996) increased plasma ACTH and glucocorticoids (Weiss et al., 1991), and alterations in peripheral immune parameters (Brown et al.,…”
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Levi, J. (2010) · cIRcle (University of British Columbia) · doi:10.14288/1.0071042
“Furthermore we also measured stomach weight to verify vagotomy as previously reported [122].”
BackgroundMethodResultInfluentialNeuroscience and Biobehavioral Reviews
Poon, D. C.-H., Ho, J. Y. S., Chiu, K., & Chang, R. C. (2013)
Cytokines and Leptin as Mediators of the Hypothalamo-Pituitary-Adrenal Axis
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Dantzer, R., Konsman, J. P., & Parnet, P. (2004) · CRC Press eBooks · doi:10.1201/9780203021941-37
Self-citationCaraway, J. (2010) · OhioLink ETD Center (Ohio Library and Information Network)
Joesting, J. J. (2013) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Weber, M. D. (2015) · CU Scholar (University of Colorado Boulder)
Defining Microbial Signatures of Gut Dysbiosis in Models of Anxiety-related Disorders
Fields, C. T. (2022) · Digital Archive @ GSU · doi:10.57709/14866301
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Zubareva, O. E., & Клименко, В. М. (2010) · Medical academic journal · doi:10.17816/maj10430-44
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Konsman, J. P., Parnet, P., & Dantzer, R. (2004) · Informa Healthcare eBooks · doi:10.1201/9780203021941.ch34
Self-citationThe Impacts of Immune Challenges on Fish Behavior and Physiology
King, T. (2022) · Louisiana State University · doi:10.31390/gradschool_dissertations.6044
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Bao, C., Xu, S., Wu, L., Zhu, X., Wang, D., Zhang, Z., Qu, C., Yin, S., Zeng, X., Zhong, J., et al. (2025) · BMC Gastroenterology · doi:10.1186/s12876-025-04547-x
“The rIFGoper plays a central role in integrating visceral sensory inputs via the vagus nerve and modulating immune and pain responses through top-down regulation [32–34].”
IL-1β engages distinct peripheral sensory circuits to suppress feeding across timePreprint
Hayes, N. W., Xia, J. L., Frydman, J. A., Duran, M. J., Gebis, K. K., Lorch, C. M., Province, H. S., Tang, E., & Beutler, L. R. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.23.707454
Metadata
- Authors
- Bluthe, R.-M., Michaud, B., Kelley, K. W., & Dantzer, R.
- Affiliations
- Inserm (FR)
- University of Illinois Urbana-Champaign (US)
- ORCID
- Dantzer, Robert
- Venue
- NeuroReport
- Published
- 1996-06
- Volume
- 7
- Issue
- 9
- Pages
- 1485-1488
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W2004070779
- Cited by
- 158
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2022: 5 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 7 · 2015: 4 · 2014: 6 · 2013: 5 · 2012: 9
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH051569, MH-51569-01A2)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- vagotomy, IL-1β, vagal afferents, social exploration, neuroimmune interactions, intracerebroventricular administration, vagus nerve
- MeSH terms
- Analysis of Variance, Animals, Appetite Depressants, Cholecystokinin, Exploratory Behavior, Injections, Intraperitoneal, Injections, Intraventricular, Interleukin-1, Male, Random Allocation, Social Behavior, Vagotomy, Vagus Nerve, Rats, Wistar, Rats
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