A comparative study of immunomodulation produced by in vitro exposure to delta opioid receptor agonist peptides

The present study assessed the direct immunomodulatory effect of a panel of synthetic peptides exhibiting delta-opioid receptor agonist activity. Murine splenic lymphocytes and peritoneal macrophages were cultured in vitro with peptides at concentrations of 0.00001-10 mu M. Assessment was made of B-cell function by quantitating cellular proliferation, T-cell function by measuring cytokine production, natural immunity by quantitating basal and cytokine-augmented natural killer (NK) cell activity, and macrophage function by production of IL-6. These peptides had minimal effects on B-cell proliferation at any concentration examined. In comparison, enhancement of cytokine production by T-helper cells occurred following exposure to several of the compounds, to a significant extent with DPDPE, DPDPE-trifluoroacetate, or deltorphin-1 and most pronounced at concentrations between 0.00001 and 0.1 mu M. Likewise, IL-6 production by macrophages was significantly augmented by exposure to these three peptides. NK cell function was significantly enhanced by in vitro exposure to several of the peptides, with enhancement generally noted at concentrations between 0.00001 and 0.01 mu M. However, some of the peptides (most notably DADLE) greatly suppressed NK cell activity. These data suggest that delta opioid agonists are broadly immunomostimulatory.