Comparison of saturable transport and extracellular pathways in the passage of interleukin-1 α across the blood-brain barrier

Abstract

Blood-borne cytokines enter the brain by transport across the blood-brain barrier (BBB) or by leakage through extracellular pathways at sites, such as circurnventricular organs (CVOs), whithout a BBB. We used radioactively labeled albumin (T-Alb) to differentiate the relative contribution of transport and extracellular pathways to the passage of interleukin-1 α ([ 125I]IL-1 α) across the BBB. The major mechanism of entry for [ 125I]IL-1α after intravenous (i.v.) injection was a saturable transport system with extracellular pathways accounting for only a small fraction of entry into brain. CVOs concentrated blood-borne [ 125I]IL-1α in a saturable manner to a much greater extent than did the cerebral cortex and cerebellum, but accounted for less that 5% of total brain uptake. After intracerebroventricular (i.c.v.) injection, [ 125I]IL-1α and T-Alb were concentrated in the CVOs, especially the median eminence, although CVOs contained less that 1% of the substances injected. Distribution after i.c.v. injection was largely due to diffusion and leakage through extracellular pathways. We conclude that after i.c.v. injection, leakage across extracellular pathways accounts for the small but concentrated amount of [ 125I]IL-1α found in CVOs. After i.v. injection, transport across the BBB accounts for the majority of [ 125I]IL-1 α in brain.