title: Chronic morphine treatment suppresses CTL-mediated cytolysis, granulation, and cAMP responses to alloantigen.
abstract: Exposure to opioid drugs (e.g., morphine) in vivo has been shown to suppress natural killer cell activity. However, the effects of in vivo exposure to opioids on cytotoxic T lymphocyte (CTL) activity has not been investigated. The administration of morphine (50.0 mg/kg, sc) to alloimmunized mice for 11 days resulted in a significant decrease in peritoneal and splenic CTL activity. Moreover, the intracellular content of serine esterases and esterase release by CD8+ effector cells from chronic morphine-treated mice was reduced compared to that of effector cells from vehicle-treated controls. In addition, the CD8+ cAMP response to alloantigen was diminished compared to CD(8+)-enriched cells from vehicle-treated animals. However, conjugate formation between effector and target and subsequent killing of target by effector cells did not reveal significant differences between vehicle- and chronic morphine-treated animals. Serum corticosterone and dehydroepiandrosterone levels were significantly lower in the chronic morphine-treated animals while proopiomelanocortin gene expression (exon 3) in splenic lymphocytes did not correlate with morphine-mediated suppression of CTL activity. These results indicate that CTL activity is sensitive to chronic morphine exposure, implicating opioids as important cofactors during viral infections in suppressing cell-mediated immunity.
authors.affiliation: Department of Microbiology, Louisiana State University Medical Center, New Orleans 70112-1393.
authors.forename: G W
authors.initials: GW
authors.lastname: Carpenter
authors.forename: H H
authors.initials: HH
authors.lastname: Garza
authors.forename: B M
authors.initials: BM
authors.lastname: Gebhardt
authors.forename: D J
authors.initials: DJ
authors.lastname: Carr
mesh_terms: D000818:Animals; D001483:Base Sequence; D003345:Corticosterone / Q000097:blood; D000242:Cyclic AMP / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003687:Dehydroepiandrosterone / Q000097:blood; D004198:Disease Susceptibility / Q000276:immunology; D004950:Esterases / Q000032:analysis; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006561:Herpes Simplex / Q000276:immunology; D007114:Immunization; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007519:Isoantigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology*; D015213:Neuroimmunomodulation; D016133:Polymerase Chain Reaction; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D013564:Sympathetic Nervous System / Q000503:physiopathology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000201:enzymology
chemical_list: D007166:Immunosuppressive Agents; D007519:Isoantigens; D003687:Dehydroepiandrosterone; D011333:Pro-Opiomelanocortin; D009020:Morphine; D000242:Cyclic AMP; D004950:Esterases; C022635:serine esterase; D003345:Corticosterone