The influence of cytokines on the integrity of the blood-brain barrier in vitro.
The effects of the cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta 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 ohm . cm2 on polycarbonate filters. Exposure of the RCEC to TNF-alpha, IL-1 beta and IL-6 induced a decline in the TEER, which could be completely abolished by 1 muM of indomethacin, a cyclooxygenase inhibitor. In addition, the effect of IL-1 beta 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.
de Vries
H E
HE
Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
Blom-Roosemalen
M C
MC
van Oosten
M
M
de Boer
A G
AG
van Berkel
T J
TJ
Breimer
D D
DD
Kuiper
J
J
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D011451:Prostaglandin-Endoperoxide Synthases