Abstract

The effects of the cytokines tumour necrosis factor-α (TNF-α), interleukin (IL) -1 β and IL-6 on the permeability of monolayers of rat cerebral endothelial cells (RCEC) were investigated to assess potential changes in the integrity of the blood-brain barrier (BBB). RCEC were cultured to tight monolayers with a trans endothelial electrical resistance (TEER) of 100–150 ω- cm 2 on polycarbonate filters. Exposure of the RCEC to TNF-α, IL-1β and IL-6 induced a decline in the TEER, which could be completely abolished by 1 μM of indomethacin, a cyclooxygenase inhibitor. In addition, the effect of IL-1β on TEER across monolayers of RCEC could be completely inhibited by IL-1 receptor antagonist. In conclusion, cytokines induce a disruption of the BBB in vitro. In this process, cyclooxygenase activation within the endothelial cells seems to play a key role.

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