MORPHINE INDUCES SEPSIS IN MICE

Gram-negative sepsis and subsequent endotoxic shock remain major healt h problems in the United States. The present study examined the role o f morphine in inducing sepsis, Mice administered morphine by the subcu taneous implantation of a slow-release pellet developed colonization o f the liver, spleen, and peritoneal cavity with gram-negative and othe r enteric bacteria, In addition, the mice became hypersusceptible to s ublethal endotoxin challenge, The effects were blocked by the simultan eous implantation of a pellet containing the opioid antagonist naltrex one. These findings show that morphine pellet implantation in mice res ults in the escape of gram-negative organisms from the gastrointestina l tract, leading to the hypothesis that morphine used postoperatively or chronically for analgesia may serve as a cofactor in the precipitat ion of sepsis and shock, In addition, morphine-induced sepsis may prov ide a physiologically relevant model of gram-negative sepsis and endot oxic shock.