SYSTEMIC CYTOKINE ADMINISTRATION CAN AFFECT BLOOD-BRAIN-BARRIER PERMEABILITY IN THE RAT

The aim of the present study was to clarify the effect of intracarotid injection of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), in terleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on the permeability of the blood-brain barrier (BBB) in the rat. A regional b lood- to-brain transfer constant (Ki) for [C-14] alpha- aminoisobutyri c acid ([C-14]AIB) and the cerebral residual blood volume were calcula ted 10 min following administration of cytokines (CKs; 1000 U/rat). Th e injection of IL-2 and IL-6 (but not of IL1 beta) induced a significa nt enhancement of Ki values for [C-14]AIB within several brain areas; conversely, when the rats were given TNF-alpha, a striking decrease in BBB permeability was observed. The cerebral regional blood volumes ap peared significantly lower in the rats injected with IL-6 than in the control animals, but markedly increased following TNF-alpha administra tion. Our findings confirm the ability of some CKs to affect the perme ability of the BBB and/or to act, probably indirectly, as vasomodulato r agents of the cerebral microvessel endothelium.