Penetration of interleukin-6 across the murine blood-brain barrier

• Published in: Neuroscience letters Vol. 179; no. 1; pp. 53 - 56
• Main Authors: Banks, William A., Kastin, Abba J., Gutierrez, Enrique G.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 26.09.1994; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood-Brain Barrier; Capillary depletion; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrospinal fluid; Cytokine; Efflux; Fundamental and applied biological sciences. Psychology; HPLC; Humans; Injections, Intraventricular; Interleukin-6 - administration & dosage; Interleukin-6 - cerebrospinal fluid; Interleukin-6 - pharmacokinetics; Mice; Recombinant Proteins - cerebrospinal fluid; Recombinant Proteins - pharmacokinetics; Regression Analysis; Saturable; Vertebrates: nervous system and sense organs; Efflux; Saturable; Cerebrospinal fluid; Capillary depletion; HPLC; Cytokine; Saturation; Biological transport; Rodentia; Central nervous system; Blood brain barrier; Interleukin 6; Vertebrata; Mammalia; Mouse; Carrier protein; Brain (vertebrata)
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/0304-3940(94)90933-4

Interleukin-6 (IL-6) can alter brain function after peripheral administration, suggesting that it, like IL-1α, IL-1β and TNF-α, might be able to cross the blood-brain barrier (BBB). We used multiple-time regression analysis to measure the unidirectional influx constant ( K i) into brain of radioactively labeled murine and human IL-6 given 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-1α or TNF-α, showing that the transport system for IL-6 is distinct from those for IL-1α and TNF-α. ∼0.2% of the dose injected i.v. entered each gram of brain. The capillary depletion method showed that most of the IL-6 taken up by brain entered the parenchyma. However, only ∼16% of the radioactivity recovered eluted as intact I-IL-6 in brain and ∼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 behind the BBB, but that susceptibility to enzymatic dagradation may limit contact time within the CNS.