Soluble interleukin-6 (IL-6) receptor augments central effects of IL-6 in vivo.
Abstract
The pleiotropic cytokine interleukin-6 (IL-6) controls both the peripheral and central components of the acute-phase response. These activities are mediated via the IL-6 membrane receptor, but probably also via agonistic soluble IL-6 receptors (sIL-6Rs). In the present study we conducted dose-response experiments with rats that were intracerebroventricularly i.c.v.) injected with recombinant human IL-6 and sIL-6R and determined body temperature, locomotor activity, food intake, and water consumption using radiotelemetry and continuous recordings of feeding and drinking. IL-6 injected i.c.v. at 1, 10, and 100 ng increased body temperature and decreased locomotor activity and food intake, but it did not affect water consumption. When 10 ng sIL-6R, which lacked detectable biological activity, was injected i.c.v. 1 h before 1 ng IL-6, the central effects of IL-6 were enhanced and prolonged, and this was not due to endotoxin contamination of the recombinant proteins. Our data suggest that IL-6 plays an important role in the regulation of body temperature, general activity, and food intake in sick animals. Moreover, we have shown for the first time that it is possible to potentiate the effects of a mediator in vivo by administration of the corresponding receptor, which is a novel pharmacological tool for increasing receptor capacity.
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The presence of sIL-6R and the short half-life of IL-6 may be critical to whether IL-6 modulates COX-2.
“It therefore seems likely that, as with CNS responses (51), the presence of sIL-6R and the short half-life of IL-6 may be critical to whether IL-6 modulates COX-2, as our data clearly show that IL-6 deficiency prevents the expression of COX-2 after the injection of TPS.”
From Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice (2003) · cites this paper as [51]
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- Authors
- Schöbitz, B., Pezeshki, G., Pohl, T., Hemmann, U., Heinrich, P. C., Holsboer, F., & Reul, J. M. H. M.
- Affiliations
- Max Planck Society (DE)
- RWTH Aachen University (DE)
- Corresponding author
- Reul, Johannes M. H. M.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 1995-05
- Volume
- 9
- Issue
- 8
- Pages
- 659-664
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2132562760
- Cited by
- 159
- References
- 22
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 1 · 2019: 6 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 9 · 2014: 4 · 2013: 3 · 2012: 4
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- interleukin-6, soluble IL-6 receptor, acute phase response, thermoregulation, locomotor activity, dietary intake, water intake, intracerebroventricular administration, receptor potentiation, cytokine receptor signaling
- MeSH terms
- Animals, Body Temperature, Drug Synergism, Eating, Fever, Humans, Injections, Intraventricular, Locomotion, Male, Recombinant Proteins, Solubility, Interleukin-6, Rats, Wistar, Receptors, Interleukin, Receptors, Interleukin-6, Rats
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