Morphine-induced degradation of the host defense barrier: Role of macrophage injury

The effect of morphine on the degradation of the host defense barrier in ra ts and mice was studied. Mice received either 3 or 11 doses of morphine. Mi ce receiving 11 doses of morphine showed gram-negative bacteremia and bacte rial growth in samples of peritoneal fluid (PF), liver, spleen, kidneys, he art, and lungs; PF and tissue samples from only 1 control mouse showed bact erial growth, and no control mice had bacteremia. Mice receiving 11 doses a lso had suppressed bone marrow macrophage colony formation. Monocytes and p eritoneal macrophages harvested from morphine-treated mice showed greater i njury than did those from control mice. Pretreatment of mice with naloxone inhibited morphine-induced macrophage injury and degradation of the host de fense barrier. In in vitro studies, morphine attenuated the killing of bact eria phagocytosed by macrophages and also facilitated their escape. This st udy indicates that morphine-induced monocyte and macrophage injury may be l inked to degradation of the host defense barrier.