POLYCHLORINATED BIPHENYL-INDUCED IMMUNE SUPPRESSION - CASTRATION, BUTNOT ADRENALECTOMY OR RU-38486 TREATMENT, PARTIALLY RESTORES THE SUPPRESSED CYTOTOXIC T-LYMPHOCYTE RESPONSE TO ALLOANTIGEN

The cytotoxic T lymphocyte (CTL) response to allogeneic P815 tumor in C57BI/6 mice is dose-dependently suppressed after treatment with 3,3', 4,4',5,5'-hexachlorobiphenyl (HxCB). Elevation of plasma corticosteron e (CS) is also observed coincident with CTL suppression. Because immun e suppression is inducible by glucocorticoid administration, the role of elevated CS was investigated as an indirect mechanism of HxCB-induc ed immunotoxicity. In multiple experiments, HxCB treatment (10 mg/kg b .w.) consistently reduced CTL activity by 70 to 85% in male mice. Adre nalectomy failed to alter the suppression of CTL activity by HxCB. How ever, the mortality rate was high (greater-than-or-equal-to 70%) in th ese experiments and plasma CS elevation persisted in HxCB-treated adre nalectomy survivors. Therefore, the use of adrenalectomized mice was i nadequate to determine whether CS elevation leads to CTL suppression a fter HxCB treatment. Daily administration of the glucocorticoid recept or antagonist ophenyly)-17-alpha-(propanyl)-estra-4,9-dien-3-one (RU 3 8486) (150 mg/kg b.w., p.o.) also failed to alter the suppression of C TL activity in HxCB-treated mice; however, spleen cellularity was sign ificantly increased, suggesting functional GCR antagonism. Male mice w ere more sensitive to HxCB-induced CTL suppression than female mice, a nd HxCB-induced plasma CS elevation was greater in male mice. Castrati on failed to reduce the elevation of plasma CS in HxCB-treated male mi ce. However, castration partially alleviated CTL suppression in HxCB-t reated male mice. Taken together, these data suggest that 1) glucocort icoid receptor antagonism does not alleviate HxCB-induced CTL suppress ion, 2) suppression of CTL may be enhanced in male mice by HxCB effect s in the testes or by an HxCB-induced altered sensitivity of the immun e system to testes-specific factors.