Blood-borne interleukin-1 alpha is transported across the endothelial blood-spinal cord barrier of mice.
1. Previous work has shown that one mechanism by which blood-borne interleukin-1 alpha (IL-1) may be able to affect the central nervous system (CNS) is by direct transport into the brain across the blood-brain barrier (BBB). The BBB of the brain consists of endothelial (between blood and interstitial fluid) and ependymal (between blood and cerebrospinal fluid) barriers. Which of these barriers IL-1 can cross has not previously been investigated. At the spinal cord, which could be the site of action for some of the effects of IL-1 such as analgesia, the BBB consists only of the endothelial barrier. 2. We show here that IL-1 labelled with 125I (I-IL) is transported across the BBB of the spinal cord by a saturable system similar to the one previously described for the brain. High performance liquid chromatography (HPLC) showed that most of the material entering the spinal cord represented intact I-IL. The BBB of the spinal cord was no more leaky to radioactively labelled albumin than the BBB of the brain and was not disrupted by 50 micrograms kg-1 of IL-1. 3. Capillary depletion showed that most of the I-IL entered the parenchymal-interstitial fluid space of the spinal cord with only a modest amount being sequestered by the endothelial cells of its BBB. 4. I-IL entered the cervical, thoracic and lumbar regions of the spinal cord equally well. I-IL entering at the brain and diffusing caudally was estimated only to account for about 1% of the total radioactivity found in the spinal cord after i.v. injection.(ABSTRACT TRUNCATED AT 250 WORDS)
Banks
W A
WA
Veterans Affairs Medical Center, New Orleans, LA 70146.
Kastin
A J
AJ
Ehrensing
C A
CA
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013116:Spinal Cord / Q000098:blood supply / Q000378:metabolism*
D007375:Interleukin-1; D011994:Recombinant Proteins