Bidirectional transport of interleukin-1 alpha across the blood-brain barrier.
Circulating interleukin-1 alpha (IL-1 alpha) has multiple effects on the central nervous system. We investigated the ability of radioiodinated IL-1 alpha (rIL-1 alpha) to cross the rodent blood-brain barrier and found its entry rate to be 43.9 times greater than that predicted by leakage alone. The rIL-1 alpha entered multiple regions of the brain, with over 40% entering at the cortex. The hypothalamus had the highest entry rate on a weight basis but only accounted for 2% of total entry. In all experiments, the entry rate of rIL-1 alpha greatly exceeded that of simultaneously injected radiolabeled albumin. The half-time disappearance of rIL-1 alpha from the brain after central injection was 21.9 min, a time that exceeds the reabsorption rate of cerebrospinal fluid. Pretreatment of animals with aluminum decreased both entry and exit rates, which is compatible with a saturable component of transport. Thus, rIL-1 alpha has access to many regions of the brain with bidirectional transport rates across the blood-brain barrier exceeding those predicted by nonspecific mechanisms.
Banks
W A
WA
Veterans Administration Medical Center, New Orelans, LA 70146.
Kastin
A J
AJ
Durham
D A
DA
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D007375:Interleukin-1 / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR
D007375:Interleukin-1