Morphine Priming Rescues High‐Dose Morphine‐Induced Biological Perturbations

In in vitro studies, macrophage morphine priming (MP; preincubation with low-dose morphine) attenuated the effects of high-dose morphine (HDM) on macrophage capabilities of killing and containment of phagocytosed bacteria. In in vivo studies, mice received either normal saline (control), HDM, or MP twice daily for 10 consecutive days. All HDM-treated mice showed a significant peritoneal bacterial leak; none of the control and only 2 of 12 mice receiving MP showed peritoneal bacterial leak. HDM-treated mice showed decreased macrophage migration into the peritoneal cavity; however, MP inhibited this effect. In in vitro studies, macrophages and bone-marrow cells harvested from HDM-treated mice showed not only enhanced apoptosis but also decreased migration across the filter of a Boyden chamber; nevertheless, MP inhibited these effects of HDM. MP also attenuated the proapoptotic effect of HDM; however, this effect was prevented by treatment with pyrrolidine derivative of dithiocarnamate, an inhibitor of nuclear factor- kappa B. These results suggest that MP provides protection against HDM-induced degradation of the host defense barrier through preservation of macrophage function.