Morphine-induced suppression of cytotoxic T lymphocyte activity in alloimmunized mice is not mediated through a naltrindole-sensitive delta opioid receptor.
The effect of chronic morphine exposure on natural killer (NK) activity in vivo and the generation of cytotoxic T lymphocytes (CTLs) in vitro and in vivo was investigated. Chronic exposure to morphine (10(-5) - 10(-11) M) in vitro had no effect on the generation of antigen-driven effector cells. However, the daily administration of morphine (50.0 mg/kg, s.c.) into alloimmunized mice (C57BL/6 into C3H/HeN) for 11 days resulted in a decrease in peritoneal and splenic CTL activity but not splenic NK activity. In addition, there was a 60% decrease in the number of thymocytes recovered from chronic morphine-treated mice compared to vehicle-treated controls. However, the overall percentage of CD4+CD8-, CD4-CD8+ and CD4+CD8+ thymocytes did not change between the two groups of treated animals. Pretreatment of the mice with the delta 1-selective antagonist, (E)-7-benzylidine-7-dihydronaltrexone (BNTX, 0.6 mg/kg, s.c.) did not block morphine-mediated suppression of splenic CTL activity but did block morphine-induced suppression of peritoneal lymphocyte CTL activity. In addition, BNTX pretreatment alone augmented splenic NK activity and such augmentation was blocked following chronic morphine exposure. In contrast, the delta-selective antagonist, naltrindole (20.0 mg/kg, s.c.), had no effect alone nor antagonized the action of morphine on CTL activity. Splenic CTL effector cells from either treated group of animals lysed their target (EL-4 lymphoma) through a Ca(2+)-dependent mechanism. Collectively, the results indicate morphine suppresses CTL activity through an indirect pathway, insensitive to naltrindole rather than through direct lymphocyte opioid receptors.
Carr
D J
DJ
Department of Microbiology, Immunology and Parasitology, Stanley S. Scott Cancer Center, LSU Medical Center, New Orleans 70112-1393, USA.
Carpenter
G W
GW
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D007694:Killer Cells, Natural; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D017465:Receptors, Opioid, delta; D004533:Egtazic Acid; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole; D002118:Calcium