SUPPRESSION OF IMMUNE FUNCTION BY NONPEPTIDIC DELTA-OPIOID RECEPTOR ANTAGONISTS

Previous studies in this laboratory and elsewhere have provided eviden ce that compounds acting as delta opioid receptor agonists exhibit mar ked immunostimulatory potential. Conversely, the delta opioid receptor antagonists have previously been shown to demonstrate immunosuppressi ve effects as assessed by proliferation of T-cells following allogenei c or xenogeneic stimulation. The present study was performed to furthe r characterize this immunosuppressive activity using the compounds ben zylidene naltrexone (BNTX), naltrindole (NTI), and naltriben (NTB). In vitro exposure to BNTX resulted in an apparent dose-related suppressi on of B-cell proliferation, cytokine production by T-helper cells, and natural killer (NK) cell activity, with statistically significant sup pression observed at concentrations between I and 10 mu M. NTI was als o immunosuppressive for all immune function parameters examined, altho ugh this compound was less active than BNTX. In vitro exposure to the structurally related compound NTB had no significant effect on any imm une function examined in this study. In all cases, immunosuppression o ccurred in the absence of any detectable alteration in cellular viabil ity, suggesting a specific immunosuppressive effect rather than overt toxicity.