title: Effect of novel non-peptidic delta opioid receptor antagonists on human T and B cell activation.
abstract: The effects of the antagonist naltrindole (NTI) on cells of the immune system have been largely studied although the mechanisms of action are still unclear. The aim of this study is to evaluate, in vitro, the immunomodulatory activity of four new delta-selective opioid compounds structurally related to naltrindole. The effects at different concentrations of these opioid antagonists on proliferative response were studied on normal human peripheral blood mononuclear cells (PBMC) stimulated with different stimuli: mitogens, the antigen PPD, the anti-CD3 monoclonal antibodies (mAb), the superantigen Staphylococcus aureus Cowan strain 1 (SAC) and alloantigens in the mixed lymphocyte cultures (MLR). The immunomodulatory capacity of these compounds was evaluated by determining the interleukin-2 (IL-2) release in mitogen activated PBMC. The present study shows that all the new delta opioid antagonists at 10(-5) M concentration are immunosuppressive. The inhibitory action is also evident at lower concentrations when anti-CD3 mAb and SAC were used as stimulators. In addition, the production of IL-2 was inhibited by the opioid treatment, but this might not be the only mechanism of action.
authors.affiliation: Department of Immunology, Istituto Superiore di Sanità, V.le Regina Elena 299, 00161 Rome, Italy. adam@iss.it
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Ambrosio
authors.forename: Lia
authors.initials: L
authors.lastname: Noviello
authors.forename: Lucia
authors.initials: L
authors.lastname: Negri
authors.forename: Helmut
authors.initials: H
authors.lastname: Schmidhammer
authors.forename: Francesca
authors.initials: F
authors.lastname: Quintieri
mesh_terms: D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D008934:Mitogens; D017465:Receptors, Opioid, delta; D009271:Naltrexone; C055382:naltrindole