PENETRATION OF INTERLEUKIN-6 ACROSS THE MURINE BLOOD-BRAIN-BARRIER

Interleukin-6 (IL-6) can alter brain function after peripheral adminis tration, suggesting that it, like IL-1 alpha, IL-1 beta and TNF-alpha, might be able to cross the blood-brain barrier (BBB). We used multipl e-time regression analysis to measure the unidirectional influx consta nt (K-i) into brain of radioactively labeled murine and human IL-6 giv en i.v. K-i values ranged from 3.05 to 4.54 (10(-4)) ml/g/min and were inhibited by unlabeled IL-6 but not IL-1 alpha or TNF-alpha, showing that the transport system for IL-6 is distinct from those for IL-1 alp ha and TNF-alpha. similar to 0.2% of the dose injected i.v. entered ea ch gram of brain. The capillary depletion method showed that most of t he IL-6 taken up by brain entered the parenchyma. However, only simila r to 16% of the radioactivity recovered eluted as intact I-IL-6 in bra in and similar to 50% in CSF after chromatographic separation by HPLC/ Sephadex, The efflux rate for IL-6 injected into the lateral ventricle of the brain suggests that it enters the blood with the reabsorption of CSF. These results suggest that blood-borne IL-6 can reach sites be hind the BBB, but that susceptibility to enzymatic degradation may lim it contact time within the CNS.