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Endothelial-Specific Knockdown of Interleukin-1 (IL-1) Type 1 Receptor Differentially Alters CNS Responses to IL-1 Depending on Its Route of Administration
Open accessAbstract
Interleukin-1 (IL-1) has been implicated as a critical mediator of neuroimmune communication. In the brain, the functional receptor for IL-1, type 1 IL-1 receptor (IL-1R1), is localized primarily to the endothelial cells. In this study, we created an endothelial-specific IL-1R1 knockdown model to test the role of endothelial IL-1R1 in mediating the effects of IL-1. Neuronal activation in the hypothalamus was measured by c-fos expression in the paraventricular nucleus and the ventromedial preoptic area. In addition, two specific sickness symptoms, febrile response and reduction of locomotor activity, were studied. Intracerebroventricular injection of IL-1 induced leukocyte infiltration into the CNS, activation of hypothalamic neurons, fever, and reduced locomotor activity in normal mice. Endothelial-specific knockdown of IL-1R1 abrogated all these responses. Intraperitoneal injection of IL-1 also induced neuronal activation in the hypothalamus, fever, and reduced locomotor activity, without inducing leukocyte infiltration into the brain. Endothelial-specific knockdown of IL-1R1 suppressed intraperitoneal IL-1-induced fever, but not the induction of c-fos in hypothalamus. When IL-1 was given intravenously, endothelial knockdown of IL-1R1 abolished intravenous IL-1-induced CNS activation and the two monitored sickness symptoms. In addition, endothelial-specific knockdown of IL-1R1 blocked the induction of cyclooxygenase-2 expression induced by all three routes of IL-1 administration. These results show that the effects of intravenous and intracerebroventricular IL-1 are mediated by endothelial IL-1R1, whereas the effects of intraperitoneal IL-1 are partially dependent on endothelial IL-1R1.
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“The CNS is affected by cytokines (97), and this can occur through a variety of different mechanisms, including direct transfer across the BBB, stimulation of CVOs, nerve stimulation, or release from infiltrating or resident immune cells, among others (98).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [97]
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Cites
Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor
Sapolsky, R., Rivier, C., Yamamoto, G., Plotsky, P., & Vale, W. (1987) · Science · doi:10.1126/science.2821621 · Cited by 1,504
Samad, T. A., Moore, K. A., Sapirstein, A., Billet, S. E., Allchorne, A. J., Poole, S., Bonventre, J. V., & Woolf, C. J. (2001) · Nature · doi:10.1038/35068566 · Cited by 1,282
Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1
Berkenbosch, F., van Oers, J., del Rey, A., Tilders, F., & Besedovsky, H. (1987) · Science · doi:10.1126/science.2443979 · Cited by 1,151
Li, Y., Liu, L., Barger, S. W., & Griffin, W. S. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-05-01605.2003 · Cited by 563
Ericsson, A., Liu, C., Hart, R. P., & Sawchenko, P. E. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903610410 · Cited by 471
Schlaeger, T. M., Bartunkova, S., Lawitts, J. A., Teichmann, G., Risau, W., Deutsch, U., & Sato, T. N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.7.3058 · Cited by 469
The Role of the Vagus Nerve in Cytokine‐to‐Brain Communication
Maier, S. F., Goehler, L. E., Fleshner, M., & Watkins, L. R. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb09569.x · Cited by 439
Cao, C., Matsumura, K., Yamagata, K., & Watanabe, Y. (1996) · Brain Research · doi:10.1016/0006-8993(96)00575-6 · Cited by 308
Lacroix, S., & Rivest, S. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70020452.x · Cited by 280
Distinct roles for CD4 and CD8 as co-receptors in antigen receptor signalling
Julius, M. H., Maroun, C. R., & Haughn, L. (1993) · Immunology Today · doi:10.1016/0167-5699(93)90282-p · Cited by 273
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Santacroce, L., Colella, M., Charitos, I. A., Domenico, M. D., Palmirotta, R., & Jirillo, E. (2023) · Metabolites · doi:10.3390/metabo13030461 · Cited by 18
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Chen, Q., Zhang, H., Li, Q., An, Y., Herkenham, M. A., Lai, W., Popovich, P. G., Agarwal, S., & Quan, N. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808261200 · Cited by 13
Self-citationDamm, J., Wiegand, F., Harden, L. M., Wenisch, S., Gerstberger, R., Rummel, C. D., & Roth, J. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.10.007 · Cited by 11
Nadjar, A., Sauvant, J., Combe, C., Parnet, P., & Konsman, J. P. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.05.005 · Cited by 10
Davis, D. S., & Carson, M. J. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4729-0_1 · Cited by 8
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Murta, V., Pitossi, F. J., & Ferrari, C. C. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.07.007 · Cited by 8
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Tang, F., Xu, F., Cui, L., Huang, W. C., Jiang, L., Chen, L., Yan, W., He, W., Shen, C., Huang, H., et al. (2020) · Journal of Molecular Histology · doi:10.1007/s10735-020-09860-1 · Cited by 6
Jin, S., Wu, X., Zhang, Y., Xu, F., Zhen, W., Sun, Y., Pan, Y., Lu, Y., Yang, Y., Sun, W., et al. (2026) · hLife · doi:10.1016/j.hlife.2026.03.001 · Cited by 6
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Blomqvist, A. G. (2024) · Temperature · doi:10.1080/23328940.2024.2401674 · Cited by 3
Hammond, B. P., Zia, S., Hahn, E., Kapustina, M., Lange, T., Friesen, S., Manek, R., Lee, K. V., Castellanos-Molina, A., Bretheau, F., et al. (2025) · Development · doi:10.1242/dev.204610 · Cited by 3
Robbins, M. K., Deer, E. M., Thompson, D. G., McKay, J., Williams, J. M., & Cornelius, D. C. (2025) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00159.2025 · Cited by 1
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Ge, S., Lin, J., Lin, W., Liu, T., Qiao, H., Yang, W., Zhu, L., Babarinde, I. A., Kang, Z., Chu, J., et al. (2026) · The Innovation Life · doi:10.59717/j.xinn-life.2026.100204 · Cited by 2
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Hamzic, N. (2013) · DiVA (Linkoping University) · Cited by 1
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Bonsall, D. R., & Harrington, M. E. (2015) · Wiley eBooks · doi:10.1002/9781118467831.ch5
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Gautron, L., & Layé, S. (2011) · Obésité · doi:10.1007/s11690-011-0278-5
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Ruud, J. (2012) · DiVA (Linkoping University)
Prostaglandin E2 in Brain-mediated Illness Responses
Elander, L. (2010) · DiVA (Linkoping University)
Inflammatory regulation of hypothalamic neurons in sickness behavior
Grossberg, A. J. (2014) · doi:10.6083/m40r9mc6
Henry, C. J. (2011) · OhioLink ETD Center (Ohio Library and Information Network)
Inflammation-Induced Gene Expression in Brain and Adrenal Gland
Engström, L. (2008) · DiVA (Linkoping University)
Hadfield, J. M. (2017) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.5731
Fever: Mediators and Mechanisms
Roth, J. (2017) · Wiley-VCH eBooks · doi:10.1002/9783527692156.ch33
Molecular Mechanisms of Reward and Aversion
Klawonn, A. M. (2017) · Linköping University medical dissertations · doi:10.3384/diss.diva-143459
Bai, D., Ma, Y., Lv, L., Wang, Y., Yang, W., & Ma, Y. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134755
RetractedInflammatory Signaling Across the Blood-Brain Barrier and the Generation of Fever
Eskilsson, A. (2020) · Linköping University medical dissertations · doi:10.3384/diss.diva-163003
Immune-to-Brain Signaling in Fever : The Brain Endothelium as Interface
Mirrasekhian, E. (2020) · Linköping University medical dissertations · doi:10.3384/diss.diva-168711
Talking to the Brain at the Blood-Brain Barrier through Inflammation-Induced Prostaglandin E2
Vasilache, A. M. (2015) · Linköping University medical dissertations · doi:10.3384/diss.diva-114378
Vincent, J. C., Garnett, C. N., Watson, J. B., Higgins, E. K., Macheda, T., Sanders, L. G., Roberts, K. N., Shahidehpour, R. K., Blalock, E. M., Quan, N., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26632489
Self-citationVincent, J. C., Garnett, C. N., Watson, J. B., Higgins, E. K., Macheda, T., Sanders, L. G., Roberts, K. N., Shahidehpour, R. K., Blalock, E. M., Quan, N., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26632492
Self-citationTerhune, T. D., Ghafourian, T., Eshraghi, R. S., Eshraghi, A. A., & Deth, R. C. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05842-8
Metadata
- Authors
- Ching, S., Zhang, H., Belevych, N., He, L., Lai, W., Pu, X.-A., Jaeger, L. B., Chen, Q., & Quan, N.
- Affiliations
- The Ohio State University (US)
- Saint Louis University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-09-26
- Volume
- 27
- Issue
- 39
- Pages
- 10476-10486
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6673171
- OpenAlex
- W2047319988
- Cited by
- 156
- References
- 39
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 9 · 2020: 10 · 2019: 4 · 2018: 7 · 2017: 16 · 2016: 9 · 2015: 13 · 2014: 18 · 2013: 7 · 2012: 10
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R01AI059089)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- interleukin-1, endothelial cells, neuroimmune interactions, hypothalamus, c-fos, paraventricular nucleus, fever, locomotor activity, leukocyte infiltration, cyclooxygenase-2, route of administration, intracerebroventricular administration, intraperitoneal injection, intravenous injection, sickness behavior
- MeSH terms
- Animals, Central Nervous System, Fever, Hypothalamus, Immunologic Factors, Interleukin-1, Mice, Transgenic, Motor Activity, Neuroimmunomodulation, Genes, fos, Endothelial Cells, Mice, Cyclooxygenase 2, Receptors, Interleukin-1 Type I
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