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Human interleukin (IL) 1 alpha, murine IL-1 alpha and murine IL-1 beta are transported from blood to brain in the mouse by a shared saturable mechanism.
Abstract
Interleukins (ILs) 1 alpha and 1 beta are important components of the neuroimmune axis. Recent work has shown that human 125I-IL-1 alpha can enter the brain from the blood by a saturable system, suggesting a mechanism that may directly link the immune and nervous systems. Here, it is shown that radioiodinated murine IL-1 beta and especially murine IL-1 alpha are even more rapidly transported into the brain of the mouse than is radioiodinated human IL-1 alpha after i.v. injection. All three cytokines exhibited self-inhibition, thus demonstrating saturable transport. Also, they all cross-inhibited the transport of each other. This shows that there are not three separate transport systems, but that they either share transport systems with overlapping affinities or share a single system. It was calculated that 0.06% to 0.08% of the dose of human 125I-IL-1 alpha injected i.v. was present in the brain during the first 60 min. By contrast, no saturable component could be detected in the brain to blood passage of the three ILs. No disruption of the blood-brain barrier to radioactively labeled albumin was found with i.v. doses of up to 50 micrograms/kg of human IL-1 alpha. Additional studies on the blood to brain transport of human 125I-IL-1 alpha showed no modification by dexamethasone, morphine, indomethacin or alpha-melanocyte stimulating hormone. Studies with antibodies directed toward the binding or nonbinding sites of IL or its receptor on the murine T lymphocyte suggest similar, but not identical, structural requirements for transport and for receptor binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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“the active transport of cytokines (Banks et al, 1991;Gutierrez et al, 1993;Plotkin et al, 1996), notably IL1, IL6, and TNF, is likely an important contributor to changes in sleep that occur during prolonged disease or infection.”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Banks et al, 1991
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Background
Metadata
- Authors
- Banks, W. A., Ortiz, L., Plotkin, S. R., & Kastin, A. J.
- Affiliations
- Veterans Health Administration (US)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1991-12
- Volume
- 259
- Issue
- 3
- Pages
- 988-996
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1892932767
- Cited by
- 474
- References
- 0
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 8 · 2023: 12 · 2022: 6 · 2021: 10 · 2020: 13 · 2019: 5 · 2018: 12 · 2017: 8 · 2016: 11 · 2015: 17 · 2014: 15 · 2013: 10 · 2012: 11
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- interleukin-1 alpha, IL-1β, blood-brain barrier, cytokine transport, saturable transport, neuroimmune axis, blood-brain barrier integrity, interleukin-1 receptor, T cells
- MeSH terms
- Animals, Antibodies, Biological Transport, Blood-Brain Barrier, Brain, Humans, Injections, Intravenous, Injections, Intraventricular, Interleukin-1, Iodine Radioisotopes, Recombinant Proteins, Mice
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