A COMPARATIVE-STUDY OF IMMUNOMODULATION PRODUCED BY IN-VITRO EXPOSURETO DELTA-OPIOID RECEPTOR AGONIST PEPTIDES

The present study assessed the direct immunomodulatory effect of a pan el of synthetic peptides exhibiting delta-opioid receptor agonist acti vity. Murine splenic lymphocytes and peritoneal macrophages were cultu red in vitro with peptides at concentrations of 0.00001-10 mu M. Asses sment was made of B-cell function by quantitating cellular proliferati on, 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 peptid es had minimal effects on B-cell proliferation at any concentration ex amined. In comparison, enhancement of cytokine production by T-helper cells occurred following exposure to several of the compounds, to a si gnificant extent with DPDPE, DPDPE-trifluoroacetate, or deltorphin-1 a nd most pronounced at concentrations between 0.00001 and 0.1 mu M. Lik ewise, IL-6 production by macrophages was significantly augmented by e xposure to these three peptides. NK cell function was significantly en hanced by in vitro exposure to several of the peptides, with enhanceme nt generally noted at concentrations between 0.00001 and 0.01 mu M. Ho wever, some of the peptides (most notably DADLE) greatly suppressed NK cell activity. These data suggest that delta opioid agonists are broa dly immunomostimulatory.