Effects of intrahippocampal infusion of interleukin-6 on passive avoidanceand nitrite and prostaglandin levels in the hippocampus in rats

Bilateral infusion of interleukin-6 (IL-6) 80 ng into the hippocampus has b een shown to impair retention of a step-through passive avoidance task via shortening the step-through latency in testing. This infusion with IL-6 als o increased the levels of nitrite and 6-ketoprostaglandin F-1 alpha (6-keto -PGF(1 alpha)) in rat hippocampus. In addition, intraperitoneal injection o f N-G-nitro-L-arginine (CAS 2149-70-4) 100 mg/kg for 5 days improved the re tention impairment induced by IL-6 and meanwhile antagonized the increase i n 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-PGF(1 alpha) levels. These results indicate that IL-6 impairs reten tion of passive avoidance probably via the overproduction of nitric oxide ( NO) and suggest that IL-6 may possess an inducible effect on NO synthase an d 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 oxid e in the brain may partially mediate the amnesic effect of IL-6.