Ma T C, Zhu X Z
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport, USA.
Arzneimittelforschung. 2000 Mar;50(3):227-31. doi: 10.1055/s-0031-1300190.
Bilateral infusion of interleukin-6 (IL-6) 80 ng into the hippocampus has been shown to impair retention of a step-through passive avoidance task via shortening the step-through latency in testing. This infusion with IL-6 also increased the levels of nitrite and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in rat hippocampus. In addition, intraperitoneal injection of NG-nitro-L-arginine (CAS 2149-70-4) 100 mg/kg for 5 days improved the retention impairment induced by IL-6 and meanwhile antagonized the increase in nitrite levels. Furthermore, intraperitoneal injection with indometacin (CAS 53-86-1) 10 mg/kg daily for 5 days reduced the IL-6-induced increase in 6-keto-PGF1 alpha levels. These results indicate that IL-6 impairs retention of passive avoidance probably via the overproduction of nitric oxide (NO) and suggest that IL-6 may possess an inducible effect on NO synthase and cyclo-oxygenase in the hippocampus. These findings support the hypothesis that central IL-6 participates in the pathogenesis of Alzheimer's disease, and the overproduction of nitric oxide in the brain may partially mediate the amnesic effect of IL-6.
向海马体双侧注射80纳克白细胞介素-6（IL-6）已被证明会通过缩短测试中的穿梭潜伏期来损害穿梭式被动回避任务的记忆保持。这种IL-6注射还会增加大鼠海马体中亚硝酸盐和6-酮-前列腺素F1α（6-酮-PGF1α）的水平。此外，腹腔注射100毫克/千克的NG-硝基-L-精氨酸（CAS 2149-70-4），持续5天，可改善由IL-6引起的记忆保持损伤，同时拮抗亚硝酸盐水平的升高。此外，每天腹腔注射10毫克/千克的吲哚美辛（CAS 53-86-1），持续5天，可降低IL-6诱导的6-酮-PGF1α水平的升高。这些结果表明，IL-6可能通过一氧化氮（NO）的过量产生损害被动回避的记忆保持，并表明IL-6可能对海马体中的一氧化氮合酶和环氧化酶具有诱导作用。这些发现支持了中枢IL-6参与阿尔茨海默病发病机制的假说，并且大脑中一氧化氮的过量产生可能部分介导了IL-6的失忆效应。
