Morphine withdrawal sensitizes mice to lipopolysaccharide: Elevated TNF-α and nitric oxide with decreased IL-12

Mice made dependent on morphine using slow-release morphine pellets for 96 h were withdrawn by removal of pellets, followed by a sublethal dose of LPS 24 h later.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 Animals withdrawn from placebo pellets receiving LPS all survived, as did morphine-withdrawn mice receiving saline. Morphine-withdrawn LPS-treated animals had elevated serum TNF-α and nitric oxide levels, and depressed IL-12 levels compared to controls. Anti-TNF-α antibody given prior to LPS challenge afforded significant protection to morphine-withdrawn animals.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