Selective depletion of immature thymocytes by oral administration of ethylene glycol monomethyl ether.
Although immunotoxicity of ethylene glycol monomethyl ether (EGME) has been strongly suspected, functional evaluation of the immune response in EGME-treated animals was negative in previous studies. We observed a decrease in thymic cellularity and increases in the various ex vivo immunological assays in mice, orally administered with EGME 0.5 or 1.0 mg/g body weight daily for 5 or 10 days: ex vivo lymphoproliferative responses to concanavalin A, in vitro induction of trinitrophenyl (TNP)-specific cytotoxic T-cell activity of thymocytes and splenocytes. Histopathological examination of the thymus of the treated mice disclosed a markedly atrophic cortex and almost intact thymic medulla. Study of thymocyte surface markers revealed that CD4+/CD8+, Thy-1+, PNA+ immature thymocytes were relatively decreased in EGME-gavaged mice and that, thus, ratios of CD4-/CD8+, H2+ mature thymocytes were enriched. These findings indicate that oral administrations of EGME selectively deplete immature thymocytes in mice. Although the mechanism of action remains unknown, the EGME-induced immature thymocyte depletion is not considered to be due to lymphocidal action of corticosteroids.
Kayama
F
F
Department of Environmental Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Yamashita
U
U
Kawamoto
T
T
Kodama
Y
Y
D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD / Q000187:drug effects; D000943:Antigens, Differentiation; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005026:Ethylene Glycols / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D005026:Ethylene Glycols; D003208:Concanavalin A; C005219:methyl cellosolve