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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Active transport of cytokines, notably IL1, IL6, and TNF, is likely an important contributor to changes in sleep during prolonged disease or infection.
“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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Luheshi, G. N. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb08316.x · Cited by 156 · see citing works
Banks, W. A. (1999) · Journal of NeuroVirology · doi:10.3109/13550289909021284 · Cited by 156 · see citing works
“However, the BBB transporter for interleukin-1a is immunologically distinct from the T-cell type I receptor (Banks et al, 1991; Banks, 1999b) and PTS-1, which transports Tyr-MIF-1 and Met-Enk, is distinguishable from the receptors for either of its peptide ligands.”
BackgroundSelf-citationPlata‐Saláman, C. R., Sonti, G., Borkoski, J. P., Wilson, C. D., & ffrench‐Mullen, J. M. H. (1996) · Physiology & Behavior · doi:10.1016/0031-9384(96)00148-5 · Cited by 158 · see citing works
Leptin neuroprotection in the CNS: mechanisms and therapeutic potentials
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Kakucska, I., Qi, Y., Clark, B. D., & Lechan, R. M. (1993) · Endocrinology · doi:10.1210/endo.133.2.8344218 · Cited by 161 · see citing works
Effects of Intestinal Microbiota on Brain Development in Humanized Gnotobiotic Mice
Lu, J. N., Lu, L., Yu, Y., Cluette‐Brown, J. E., Martin, C. R., & Claud, E. C. (2018) · Scientific Reports · doi:10.1038/s41598-018-23692-w · Cited by 146 · see citing works
Permeation of Growth Hormone across the Blood-Brain Barrier
Pan, W., Yu, Y., Cain, C. M., Nyberg, F., Couraud, P. O., & Kastin, A. J. (2005) · Endocrinology · doi:10.1210/en.2005-0587 · Cited by 149 · see citing works
Self-citationGabellec, M., Griffais, R., Fillion, G., & Haour, F. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(95)00042-q · Cited by 145 · see citing works
Banks, W. A., Jumbe, N. L. ‘., Farrell, C. L., Niehoff, M. L., & Heatherington, A. C. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.10.035 · Cited by 145 · see citing works
Self-citationPeptides crossing the blood–brain barrier: some unusual observations
Kastin, A. J., Pan, W., Maness, L. M., & Banks, W. A. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01961-7 · Cited by 144 · see citing works
Self-citationHypothalamic inflammation and energy homeostasis: Resolving the paradox
Thaler, J. P., Choi, S. J., Schwartz, M. W., & Wisse, B. E. (2010) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2009.10.002 · Cited by 144 · see citing works
“However, the origin of these cytokines remains controversial as peripheral cytokines can both enter the brain directly [1,50] and be produced locally by microglia – the resident immune cells in the CNS – as well as by neurons [52,31].”
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Tumor necrosis factor and stroke: Role of the blood–brain barrier
Pan, W., & Kastin, A. J. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.07.008 · Cited by 140 · see citing works
“During the past two decades, specific transport systems for selective proinflammatory cytokines and neurotrophic proteins have also been identified at the BBB (Banks et al., 1991; Pan and Kastin, 2003).”
BackgroundSelf-citationInterleukin-1β inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C
Plata‐Saláman, C. R., & ffrench‐Mullen, J. M. H. (1994) · European Journal of Pharmacology Molecular Pharmacology · doi:10.1016/0922-4106(94)90202-x · Cited by 137 · see citing works
- 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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