[Background] The blood brain barrier (BBB) primarily composed of a monolayer of brain microvascular endothelial cells (BMECs) functions to limit the transfer of materials from the circulating blood to the brain parenchyma. We previously reported that treatment with leukemia inhibitory factor (LIF) and oncostatin M (OSM), both of which are IL-6 family cytokines, attenuated the BBB function, whereas IL-6 did not affect it. Our previous study showed that expression of IL-6 receptor (IL-6R) mRNA was much weaker than those of LIF and OSM receptors. However, IL-6R has been reported to have two forms, that is, membrane-bounded and soluble forms. Therefore, in this study, we examined the effect of co-treatment of IL-6 with soluble IL-6R (sIL-6R) on the BBB function and compared it with the effects of LIF, OSM and IL-6 alone.
[Methods] BMECs were prepared from the brain of C57/B6 mice. In vitro BBB model was prepared by seeding BMECs onto Transwell inserts, and treated with IL-6, sIL-6R, IL-6+sIL-6R, LIF or OSM. Barrier function was evaluated by measuring transendothelial electrical resistance (TEER). 
[Results] IL-6+sIL-6R, but not IL-6 alone, decreased the BBB function. Among these cytokines, BBB function-attenuating effects were in the order of OSM > IL-6+sIL-6R = LIF at a concentration of 100 ng/mL and OSM > IL-6+sIL-6R > LIF at a concentration of 300 ng/mL.