title: Aspects of dioxin toxicity are mediated by interleukin 1-like cytokines.
abstract: Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) results in a broad spectrum of toxic effects. Most, if not all, of these responses are dependent upon the binding of dioxin to the aryl hydrocarbon receptor. Given their common roles in chemically induced toxicity, we asked whether interleukin 1 (IL1)-like cytokines play a role in acute aspects of the dioxin response. To test this idea, we employed a "triple-null" mouse model that lacks the two receptors for the tumor necrosis factors-alpha and -beta and the receptor for the IL1-alpha and IL1-beta cytokines. When triple null mice were treated with dioxin, there was significant attenuation in the levels of serum alanine aminotransferase, signifying reduced hepatocellular damage. In addition, the triple-null mice were protected from dioxin-induced liver inflammation. Loss of receptors for the IL1-like cytokines was not protective for all aspects of dioxin toxicity. Endpoints such as thymic involution, Cyp1a2 induction, hepatomegaly, and hydropic degeneration remain unchanged in this model.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, 53706-1599, USA.
authors.forename: Kalyan
authors.initials: K
authors.lastname: Pande
authors.forename: Susan M
authors.initials: SM
authors.lastname: Moran
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Bradfield
mesh_terms: D000818:Animals; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004147:Dioxins / Q000633:toxicity*; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D004147:Dioxins; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor