In a series of studies of the immunobiological sequelae 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 less than 0.001) vs. untreated PBMC. The inhibitory effects of DES or
leuprolide were not due to cytotoxicity since the viability 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 observations 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.(ABSTRACT TRUNCATED AT 250 WORDS)