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Acute ANIT toxicity in male IL-10 knockout and wild-type mice
Brenda Faiola1, Richard A Peterson, Carrie L Kimbrough
1RTI International, Discovery Sciences, Research Triangle Park, North Carolina, USA.
Abstract:
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.
Insights
Interleukin-10 (IL-10) knockout mice showed less liver injury but more biliary damage after toxicant exposure. This suggests IL-10 plays a complex role in the innate immune response to liver injury.
Area of Science:
- Toxicology
- Immunology
- Hepatology
Background:
- The innate immune response influences toxicant-induced liver injury.
- Interleukin-10 (IL-10) is a key mediator in innate immunity.
- Its specific role in toxicant-induced biliary epithelium injury remains unclear.
Purpose of the Study:
- To investigate the role of IL-10 in the injury and repair of biliary epithelium following toxicant exposure.
- To compare hepatocellular and biliary injury in wild-type (WT) and IL-10 knockout (KO) mice.
Main Methods:
- WT and IL-10 KO mice received a single toxic dose of alpha-napthylisothiocyanate (ANIT).
- Mice were assessed for clinical signs, hepatocellular injury, and biliary epithelium changes over four days.
- Histological analysis evaluated inflammation, necrosis, and proliferation.
Main Results:
- ANIT-treated IL-10 KO mice exhibited less hepatocellular injury compared to WT mice.
- However, IL-10 KO mice showed increased biliary epithelial inflammation and necrosis.
- Biliary and hepatocyte proliferation was enhanced in IL-10 KO mice, indicating a heightened reparative response.
Conclusions:
- IL-10 deficiency results in reduced hepatocellular injury but exacerbated biliary epithelial damage after ANIT exposure.
- These findings suggest a complex, dual role for IL-10 in modulating toxicant-induced liver injury and repair.
