COMPARISON OF SATURABLE TRANSPORT AND EXTRACELLULAR PATHWAYS IN THE PASSAGE OF INTERLEUKIN-1-ALPHA ACROSS THE BLOOD-BRAIN-BARRIER

Blood-borne cytokines enter the brain by transport across the blood-br ain barrier (BBB) or by leakage through extracellular pathways at site s, such as circumventricular organs (CVOs), whithout a BBB. We used ra dioactively labeled albumin (T-Alb) to differentiate the relative cont ribution of transport and extracellular pathways to the passage of int erleukin-1 alpha ([I-125]IL-1 alpha) across the BBB. The major mechani sm of entry for [I-125]IL-1 alpha after intravenous (i.v.) injection w as a saturable transport system with extracellular pathways accounting for only a small fraction of entry into brain. CVOs concentrated bloo d-borne [I-125]IL-1 alpha in a saturable manner to a much greater exte nt than did the cerebral cortex and cerebellum, but accounted for less that 5% of total brain uptake. After intracerebroventricular (i.c.v.) injection, [I-125]IL-1 alpha 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 la rgely due to diffusion and leakage through extracellular pathways. We conclude that after i.c.v. injection, leakage across extracellular pat hways accounts for the small but concentrated amount of [I-125]IL-1 al pha found in CVOs. After i.v. injection, transport across the BBB acco unts for the majority of [I-125]IL-1 alpha in brain.