Regulation of human B lymphocyte activation by opioid peptide hormones - Inhibition of IgG production by opioid receptor class (mu-, kappa-, and delta-) selective agonists

Opioid peptides have been reported by many laboratories to modulate in vitro and in vivo cell-mediated and humoral immune responses. However, less attention has been afforded to the class or classes of opioid receptors involved in these immunomodulatory effects. Previous studies by this laboratory indicated that beta-endorphin and methionine-enkephalin were potent inhibitors of Staphylococcus aureus, Cowen strain I (SAC)-induced IgG production by human B lymphocytes. Results obtained from the present studies indicate that, at pharmacological concentrations, mu-, delta-, and kappa-receptor-selective agonists are potent inhibitors of SAC-induced IgG-secreting cells (IgG-ISC) by human B lymphocytes. Moreover, the suppression of IgG-ISC formation was reversed by mu- delta- and kappa-receptor class-selective antagonists, [D'Tic]cTAP, ICI 174,864, and nor-BNI, respectively. These findings are in agreement with other studies showing that more than one class of receptors are involved in opioid peptide-mediated immunoregulation. Additional studies indicated that all three class-selective receptor agonists were found to suppress SAC-induced IL-6 production in intact PBMC cultures. As observed for suppression of IgG-ISC formation, inhibition of IL-6 production was found to be reversed by the appropriate receptor class-selective antagonist. These results support the hypothesis that one mechanism of opioid peptide-mediated inhibition of antibody production is via the down regulation of cytokine synthesis.