EFFECT OF MORPHINE AND METHADONE ACUTE TREATMENT ON IMMUNOLOGICAL ACTIVITY IN MICE - PHARMACOKINETIC AND PHARMACODYNAMIC CORRELATES

This report describes the 24-hr time course of the immunomodulatory ef fects of an acute s.c. injection of morphine in C57BL6 mice, and corre lates these effects with the drug's analgesic properties and serum lev els. Acute morphine treatment had a biphasic effect on various immune parameters: there was an increase in in vitro phagocytosis and the kil ling of Candida Albican cells by peritoneal polymorphonuclear leukocyt es 20 and 40 min after the injection of morphine, 20 mg/kg, when analg esia and serum morphine concentrations were at their peak. Interesting ly, 24 hr after morphine administration (when antinociception and morp hine blood levels were no longer detectable) these parameters underwen t a marked reduction. Similarly, macrophage-mediated inhibition of tum or cells proliferation was first stimulated (at 20 and 40 min) and the n depressed (at 24 hr). Splenic natural killer cell cytotoxicity, dete rmined by standard Cr-51 release from YAC-1 target cells, also was eva luated. No differences in natural killer activity was observed at any of the monitored time points. In addition, we evaluated the immunomodu latory effects of an acute injection of methadone (a synthetic narcoti c compound) at a dose inducing the same degree of analgesia as morphin e. None of the tested immunoparameters were affected by the administra tion of methadone, which indicates the different drug-sensitivity of i mmunological correlates in vivo.