Acute ANIT toxicity in male IL-10 knockout and wild-type mice.
The innate immune response is known to modify hepatocellular injury induced by toxicants. To assess the role of IL-10, a component of the innate immune response, in toxicant-induced injury of biliary epithelium, wild-type (WT) and IL-10 knockout mice (KO) were given a single toxic dose (50 mg/kg) of alpha-napthylisothiocyanate (ANIT) and assessed at twenty-four-hour intervals for four days following treatment. Clinical signs of toxicity were greater in WT mice. Unexpectedly, over the course of the study, there was a consistent tendency for ANIT-treated IL-10 KO mice to have less hepatocellular injury than WT mice. However, changes in the biliary epithelium differed in that there was more histologic evidence of inflammation and necrosis on days 2 and 3, respectively, in ANIT-treated IL-10 KO mice compared with WT mice. Proliferation of biliary epithelium and hepatocytes was greater and/or occurred earlier in the ANIT-treated IL-10 KO mice compared with the ANIT-treated WT mice, suggesting a greater reparative response was needed for recovery after toxicant injury in the IL-10 KO mice. Overall, our data suggest that IL-10 KO mice have less hepatocellular injury than WT mice following a toxic dose of ANIT and that biliary epithelial injury is accentuated in the KO mice.
Faiola
Brenda
B
RTI International, Discovery Sciences, Research Triangle Park, North Carolina, USA.
Peterson
Richard A
RA
Kimbrough
Carrie L
CL
Jordan
Holly L
HL
Cullen
John M
JM
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005704:Gallbladder / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics*; D017879:Isothiocyanates / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D017879:Isothiocyanates; D016753:Interleukin-10; C037152:isothiocyanic acid