Last year we found that regulatory T cells infiltrated into the liver of female Balb/cJ mice following halothane treatment and inhibited both humoral and cellular immune reactions against trifluoroacetylated proteins formed in vivo following halothane treatment. This year we report that newly discovered myeloid-derived suppressor cells also infiltrated into the liver of female Balb/cJ mice following halothane treatment. These cells have be shown recently to inhibit effector T cell activity in tumors, infections, and in autoimmune diseases. Conclusion: These findings suggest that both regulatory T cells and myeloid-derived suppressor cells might have a role in preventing drug-protein adducts from causing liver injury mediated by the adaptive immune system and that deficiencies in the activities of these regulatory cells might be susceptibility factors in DILD.

Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2011
Total Cost
$495,446
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