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Abstract
<p class="first" id="d2593656e67">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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