Abstract
Mice made dependent on morphine using slow-release morphine pellets for 96 h were withdrawn by removal of pellets, followed by a sublethal dose of LPS 24 h later. These animals exhibited 100% lethality. Animals withdrawn from placebo pellets receiving LPS all survived, as did morphine-withdrawn mice receiving saline. Morphine-withdrawn LPS-treated animals had elevated serum TNF-α and nitric oxide levels, and depressed IL-12 levels compared to controls. Anti-TNF-α antibody given prior to LPS challenge afforded significant protection to morphine-withdrawn animals. These studies show that morphine withdrawal sensitizes to LPS lethality via increased production of TNF-α.
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