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Interleukin-1 alpha in blood has direct access to cortical brain cells
W A Banks1, A J Kastin, E G Gutierrez
1Veterans Affairs Medical Center, New Orleans, LA 70146.
Insights
Circulating Interleukin-1 alpha (IL-1 alpha) directly enters the brain
Area of Science:
- Neuroscience
- Immunology
- Physiology
Background:
- Interleukin-1 alpha (IL-1 alpha) is an immune protein affecting the central nervous system (CNS).
- The blood-brain barrier (BBB) typically restricts protein entry into the brain and cerebrospinal fluid (CSF).
Purpose of the Study:
- To investigate the direct entry mechanism of IL-1 alpha into the CNS across the BBB.
- To determine if IL-1 alpha can cross the BBB intact and influence brain function.
Main Methods:
- Used selective interleukin receptor antagonist (IL-1ra).
- Employed capillary depletion method, high-performance liquid chromatography (HPLC).
- Utilized saturation experiments with unlabeled IL-1 alpha and radioactive labeling.
Main Results:
- Radioactively labeled IL-1 alpha injected intravenously (iv) entered the CNS in intact form.
- IL-1 alpha crossed the BBB into the brain cortex and CSF, areas lacking circumventricular organs or capillaries.
- Capillary sequestration of IL-1 alpha occurred in a saturable manner, suggesting carrier-mediated transport.
Conclusions:
- Circulating IL-1 alpha has direct access to the brain, including cortical cells, bypassing the BBB.
- A saturable transport system facilitates IL-1 alpha entry into the CNS.
- This pathway represents a significant route for brain-immune system interaction.
Abstract:
Interleukin-1 alpha (IL-1 alpha), an immunoregulatory protein secreted by the peripheral immune system, affects the central nervous system (CNS). IL-1 alpha could directly enter the parenchyma of the brain in intact form to alter brain function, or it could be blocked or sequestered by the capillary bed comprising the blood-brain barrier (BBB) that normally retards entry of circulating proteins to the brain and cerebrospinal fluid (CSF). We show here by use of the selective interleukin receptor antagonist (IL-1ra), capillary depletion method, high performance liquid chromatography (HPLC) and saturation with unlabeled IL-1 alpha that radioactively labeled IL-1 alpha injected iv directly enters the CNS in intact form. This also occurs in the brain cortex, an area devoid of circumventricular organs (CVOs), and in the CSF, an area devoid of capillaries. Capillaries can also sequester IL-1 alpha in a saturable manner, suggesting that they may be the site for the carrier-mediated entry of IL-1 alpha into the CNS. Thus, the results show that circulating IL-1 alpha has direct access to cortical brain cells behind the BBB through a saturable transport system that provides a major pathway by which the brain and immune system interact.
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