Modification of Lymphocyte Responsiveness by Hormones Used in the Treatment of Urologic Malignancies

Publisher Website
Google Scholar
Abstract
Recognition that the immune system may be important in regulating the clinical evolution of tumors and that corticosteroids suppress immune responses lends relevance to determining the concentrations in which sex hormones, currently used in the treatment of urologic malignancies, exert immunosuppressive effects. The effects of the sex hormones diethylstilbestrol, diethylstilbestrol diphosphate, testosterone and progesterone on in vitro [human] lymphocyte blastogenesis as determined by 3H thymidine incorporation after stimulation with phytomitogens and alloantigens were investigated and compared with the effects of cortisol. Compared to cortisol these sex hormones are relatively weak suppressors of lymphocyte blastogenesis (cortisol 10-7 M, progesterone 5 .times. 10-6 M, testosterone 5 .times. 10-5 M, diethylstilbestrol 5 .times. 10-5 M and diethylstilbestrol diphosphate 10-3 M) and probably are not significantly immunosuppressive in commonly used pharmacologic dosages. Similar results were observed with the T [thymus-derived] lymphocyte mitogens, phytohemagglutinin and concanavalin A and in the combined T and B [bone marrow-derived] cell mitogen, pokeweed. The fact that alloantigen-stimulated lymphocyte blastogenesis was suppressed by diethylstilbestrol indicates that sex hormones exert their effects on the lymphocytes and not on the mitogens. Sex hormones were not cytotoxic to lymphocytes. The sex hormones tested may act by suboptimal binding to glucocorticoid receptors in the lymphocytes, and the relative immunosuppressive potency of a given hormone may be related to its affinity for the glucocorticoid receptor.