Polychlorinated biphenyl-induced immune suppression: castration, but not 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 C57bl/6 mice is dose-dependently suppressed after treatment with 3,3',4,4',5,5'-hexachlorobiphenyl (HxCB). Elevation of plasma corticosterone (CS) is also observed coincident with CTL suppression. Because immune suppression is inducible by glucocorticoid administration, the role of elevated CS was investigated as an indirect mechanism of HxCB-induced immunotoxicity. In multiple experiments, HxCB treatment (10 mg/kg b.w.) consistently reduced CTL activity by 70 to 85% in male mice. Adrenalectomy failed to alter the suppression of CTL activity by HxCB. However, the mortality rate was high (> or = 70%) in these experiments and plasma CS elevation persisted in HxCB-treated adrenalectomy survivors. Therefore, the use of adrenalectomized mice was inadequate to determine whether CS elevation leads to CTL suppression after HxCB treatment. Daily administration of the glucocorticoid receptor antagonist 17-beta-hydroxy-11-beta-(4-dimethylaminophenyl)-17-alpha-(propanyl )-estra- 4,9-dien-3-one (RU 38486) (150 mg/kg b.w., p.o.) also failed to alter the suppression of CTL activity in HxCB-treated mice; however, spleen cellularity was significantly increased, suggesting functional GCR antagonism. Male mice were more sensitive to HxCB-induced CTL suppression than female mice, and HxCB-induced plasma CS elevation was greater in male mice. Castration failed to reduce the elevation of plasma CS in HxCB-treated male mice. However, castration partially alleviated CTL suppression in HxCB-treated male mice.(ABSTRACT TRUNCATED AT 250 WORDS)
De Krey
G K
GK
College of Veterinary Medicine, Oregon State University, Corvallis.
Baecher-Steppan
L
L
Deyo
J A
JA
Smith
B
B
Kerkvliet
N I
NI
D000315:Adrenalectomy; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D007165:Immunosuppression Therapy; D007519:Isoantigens / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015735:Mifepristone / Q000494:pharmacology; D009919:Orchiectomy; D010052:Ovariectomy; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D012044:Regression Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
D007519:Isoantigens; D015735:Mifepristone; D011078:Polychlorinated Biphenyls