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 I-125 (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 mu g 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. These results show that I-IL is able to cross the endothelial part of the BBB and that bloodborne IL-1 has direct access to the spinal cord.