Poster session

[P3-3-22] Effect of benzodiazepine receptor ligand on interleukin-2 and interleukin-10 production by stimulated mouse splenocytes

〇Masako Kamiya¹, Eiji Takayama ², Harumi Kawaki², Naoki Umemura², Kyohei Ueno², Moe Takahashi³, Yasunori Muramatsu³, Nobuo Kondoh⁴ (1. Chem Lab, Asahi Univ Sch Business Admin, 2. Dept Oral Biochem, Asahi Univ Sch Dent, 3. Dept Oral Maxillofac Surg, Asahi Univ Sch Dent, 4. Chem Lab, Asahi Univ Sch Dent)

Keywords:ミダゾラム、ベンゾジアゼピン受容体、インターロイキン-10

We have reported that midazolam suppressed interleukin (IL)-2 and IL-10 production from T lymphocyte-specific receptor-stimulated splenocytes in vitro. In this study, we investigated the effects of central and peripheral benzodiazepine receptor (BZPR) antagonists on IL-2 and IL-10 production by stimulated mouse splenocytes. Suppressive effect of midazolam began to be observed at a very low concentration of 0.2 μg/ml, and at 5 μg/ml, IL-2 and IL-10 production decreased to approximately 5% (IL-2) and approximately 20% (IL-10) of controls. With addition of a central BZPR antagonist, flumazenil (0.15-75 μM) to the cultures, IL-2 and IL-10 production was as the same level of controls (DMSO as solvent). The suppressive effect of midazolam was not reversed. On the other hand, addition of a peripheral BZPR antagonist, Pk11195 (0.15 to 75 μM) to a culture system containing midazolam, did not restore the effect of midazolam, but rather further reduced IL-2 and IL-10 production in a dose-dependent manner. Pk11195 inhibited IL-2 and I-10 production even without the addition of midazolam.These results suggest that suppressive effect of midazolam is not mediated by BZPR, and that there may be another regulatory pathway of IL-2 and IL-10 production in splenocytes, involving peripheral BZPR .