In vitro effects of diethylstilboestrol and the LHRH analogue leuprolide on natural killer cell activity

In a series of studies of the immunobiological sequekae of oestrogens, the in-vitro effect of diethystilboestrol (DES) and the luteinizing-hormone-releasing-hormone leuprolide (Lupron) on the lytic activity of natural killer (NK) cells have been evaluated. Ficoll-Hypaque gradient-isolated human peripheral blood mononuclear cells (PBMC) were pre-incubated with varying concentrations of DES and leuprolide and the degree of lysis for the human erythroleukemia K-562 cell line was evaluated in a 51Cr-release assay. PBMC pre-incubated with DES exhibited an 82% reduction in the ability of NK cells to lyse K-562 target cells compared with a negligible 3% increase with leuprolide (p < 0.001) vs. untreated PBMC. The inhibitory effects of DES or leuprolide were not due to cytotoxicity since the vaability of PBMC incubated for 18 and 24 h (corresponding to the DES/leuprolide preincubation time and the NK cell assay, respectively) was comparable to that of untreated (control) cells. These observatiobs demonstrate the further suppressive effects of DES on components of immunosurveillance. Pending evaluation of the effect of leuprolide on the activity of NK cells for other target cells, and other parameters of immunologic responsiveness, leuprolide may prove to be a favorable alternative to DES, both in view of its reduced clinical side-effects, and because of the suggested absence of deleterious effects to the immune system. Maintenance of tumour-host equilibrium, and some degree of immunocompetency, in the presence of effective therapy with leuprolide, may prove beneficial in achieving more effective therapy in prostate cancer patients. Possibly contra-indicated by DES-induced immunosuppression, effective therapy with leuprolide may permit the further option of adjuvant immunotherapy in some patients with prostate cancer.