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.