IN-VITRO EXPOSURE TO PEPTIDIC DELTA-OPIOID RECEPTOR ANTAGONISTS RESULTS IN LIMITED IMMUNOSUPPRESSION

Previous studies by our group have demonstrated that in vitro exposure to delta-opioid receptor agonists results in a significant immunostim ulation, whereas in vitro exposure to non-peptidic delta-opioid recept or antagonists results in significant suppression of various immune fu nctions. The present study assessed potential immunomodulation by the peptidic delta-opioid receptor antagonists TIPP, D-TIPP, and ICI 17486 4 using a panel of in vitro immune function assays. Splenocytes from f emale B6C3F1 mice were cultured with the peptides at concentrations of 0.00001-10 mu M. B cell proliferation was quantified following cellul ar activation, T cell function was assessed by cytokine production fol lowing stimulation with anti-CD3 monoclonal antibody, natural immunity was assessed by quantitating natural killer (NK) cell activity follow ing a 24-h exposure, and macrophage function was assessed by quantific ation of interleukin-6 (IL-6) production. None of the peptides examine d significantly affected B cell proliferation. Production of IL-2 by T cells was not consistently affected by exposure to either TIPP or D-T IPP, but was significantly suppressed at 10 mu M ICI 174864. Productio n of IL-4, however, was significantly suppressed by low concentrations of either TIPP or D-TIPP, and by 10 mu M ICI 174864. IL-6 production by macrophages was unaffected except for sporadic incidents of enhance d production in cells exposed to ICI 174864. NK cell function exhibite d a differential pattern of suppression, with the greatest degree of s uppression observed following exposure to TIPP and only slight suppres sion in cells exposed to either D-TIPP or ICI 174864. These data sugge st that peptidic delta-opioid receptor antagonists do not exhibit the same pattern or degree of immunosuppressive activity as the non-peptid ic antagonists at equivalent in vitro concentrations.