Effects of intrahippocampal infusion of interleukin-6 on passive avoidance and nitrite and prostaglandin levels in the hippocampus in rats.
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.
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Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport, USA.
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D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007267:Injections; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D009573:Nitrites / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D015850:Interleukin-6; D009419:Nerve Tissue Proteins; D009573:Nitrites; D011453:Prostaglandins; D019335:Nitroarginine; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat