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Natural killer (NK) cells are important in surveillance against malignant cells. The activity of NK cells can be modulated by naturally occurring mediators; interferon, interleukin-2, and hormones. Low-dose aminoglutethimide (Ag 250 mg/day) inhibits the peripheral aromatization of androstenedione hence decreasing circulating estrogens. Of ten patients treated, seven were evaluable. There was a statistically significant increase in NK activity (P = 0.0025) following the administration of Ag. There was no consistent shift in NK cell number (Leu-11b positive cells). In vitro Ag did not alter NK activity whereas 17-beta-estradiol did. These data are consistent with an indirect effect of Ag on NK activity. Hence in vivo Ag which causes a reduction in serum estrogens in postmenopausal patients, also induces an increase in NK activity.

Chronic exposure of hemophiliacs to allogeneic proteins via factor VIII concentrate for control of bleeding could lead to a state of chronic antigen stimulation. Immune function from eight hemophiliacs requiring large amounts of factor VIII concentrate was assessed. It was found that 5 of 8 had a positive blastogenic response to low concentrations of factor VIII in a 7-day thymidine uptake assay. Separation of lymphocyte subpopulations indicated that the reactivity was contained in the T cell-enriched fraction. There was no blast transformation noted secondary to the factor VIII product in 20 controls tested in a 7-day assay nor was there any mitogenic effect of the factor VIII in a 3-day assay. In fact, high concentrations of factor VIII impaired that T lymphocytes from hemophiliacs are antigenically primed to some constituent in the lyophilized factor VIII concentrate.

Chronic exposure of hemophiliacs to allogeneic proteins via factor VIII concentrate for control of bleeding could lead to a state of chronic antigen stimulation. Immune function from eight hemophiliacs requiring large amounts of factor VIII concentrate was assessed. It was found that 5 of 8 had a positive blastogenic response to low concentrations of factor VIII in a 7-day thymidine uptake assay. Separation of lymphocyte subpopulations indicated that the reactivity was contained in the T cell-enriched fraction. There was no blast transformation noted secondary to the factor VIII product in 20 controls tested in a 7-day assay nor was there any mitogenic effect of the factor VIII in a 3-day assay. In fact, high concentrations of factor VIII impaired that T lymphocytes from hemophiliacs are antigenically primed to some constituent in the lyophilized factor VIII concentrate.