We have previously found that regulatory T cells and myeloid-derived suppressor cells infiltrated into the liver of female mice following halothane treatment and appeared to have tolerogenic activity preventing halothane to cause an adaptive immune response against the liver. This year we report that several other potentially tolerogenic cells enter the liver after halothane treatment. Conclusion: These findings suggest that multiple tolerogenic cells play a role in preventing drugs from cause adaptive immune reactions against the liver. Blocking the activities of these cells may allow the development of animal models for testing the potential of new for causing adaptive immune toxicities against the liver.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$695,282
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Proctor, William R; Chakraborty, Mala; Fullerton, Aaron M et al. (2014) Thymic stromal lymphopoietin and interleukin-4 mediate the pathogenesis of halothane-induced liver injury in mice. Hepatology 60:1741-52
Proctor, William R; Chakraborty, Mala; Chea, Lynette S et al. (2013) Eosinophils mediate the pathogenesis of halothane-induced liver injury in mice. Hepatology 57:2026-36
Masson, Mary Jane; Collins, Lindsay A; Pohl, Lance R (2010) The role of cytokines in the mechanism of adverse drug reactions. Handb Exp Pharmacol :195-231