Passage of cytokines across the blood–brain barrier
Abstract
One mechanism by which blood-borne cytokines might affect the function of the central nervous system (CNS) is by crossing the blood-brain barrier (BBB) for direct interaction with CNS tissue. Saturable transport systems from blood to the CNS have been described for interleukin (IL)-1α IL-1β IL-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor-α (TNF-α). Blood-borne cytokines have been shown to cross the BBB to enter cerebrospinal fluid and interstitial fluid spaces of the brain and spinal cord. IL-2 does not cross the BBB by a saturable transport system. The blood-to-brain uptakes of IL-1α, IL-β, and IL-1ra are interrelated for most brain sites, but the posterior division of the septum shows selective uptake of blood-borne IL-1α. The saturable transport systems for IL-6 and TNF-α are distinguishable from each other and from the IL-1 systems. The amount of blood-borne cytokines entering the brain is modest but comparable to that of other water-soluble compounds, such as morphine, known to cross the BBB in sufficient amounts to affect brain function. CNS to blood efflux of cytokines has also been shown to occur, but the mechanism of passage is unclear. Taken together, the evidence shows that passage of cytokines across the BBB occurs, providing a route by which blood-borne cytokines could potentially affect brain function.
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Cytokines released by peripheral immune cells or adipose tissue can access the CNS to initiate local immune activation by several mechanisms including passage through leaky BBB at circumventricular organs, active uptake across BBB, local actions at peripheral vagal nerve afferents, activation of endothelial cells and perivascular macrophages, and recruitment of activated immune cells.
“Cytokines released by peripheral immune cells or adipose tissue can access the CNS to initiate local immune activation by several mechanisms, including 1.) passage through leaky regions in the blood-brain-barrier at circumventricular organs”
From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Banks et al., 1995
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- Authors
- Banks, W. A., Kastin, A. J., & Broadwell, R. D.
- Affiliations
- Tulane University (US)
- United States Public Health Service (US)
- ORCID
- Banks, William A.
- Venue
- Neuroimmunomodulation
- Publisher
- S. Karger AG
- Published
- 1996-03-08
- Volume
- 2
- Issue
- 4
- Pages
- 241-248
- ISSN
- 1021-7401 (ISSN-L)
- 1423-0216
- OpenAlex
- W1993537924
- Cited by
- 778
- References
- 0
- Citations by year
- 2026: 20 · 2025: 34 · 2024: 36 · 2023: 46 · 2022: 36 · 2021: 62 · 2020: 49 · 2019: 33 · 2018: 40 · 2017: 34 · 2016: 34 · 2015: 19 · 2014: 30 · 2013: 28 · 2012: 20
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImmunoModulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- blood-brain barrier, cytokine transport, interleukin-1 alpha, IL-1β, interleukin-1 receptor antagonist, interleukin-6, TNF-α, interleukin-2, saturable transport, cerebrospinal fluid, brain uptake, neuroinflammation
- MeSH terms
- Animals, Blood-Brain Barrier, Neuroimmunomodulation, Cytokines
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