In this report, we compared the adaptive immune responses following halothane treatment of normal female Balb/cJ mice to Balb/cJ mice depleted of regulatory T cells. Mice depleted of regulatory T cells had significantly higher serum levels of anti-TFA-protein antibodies and elevated T cell proliferation when treated in culture with TFA-protein adducts as compared to normal Balb/cJ mice. Moreover, there was a significant infiltration of TGF-beta-producing T regulatory cells into the liver of normal Balb/cJ mice following halothane treatment. These results suggest that T regulatory cells may have an important inhibitory effect on the adaptive immune system reaction against protein adducts of drugs released from damaged hepatocytes and immunopathology against the liver. Conclusion: These preliminary findings warrant further studies into the role of regulatory T cells in the mechanisms and susceptibility to DILD.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2010
Total Cost
$296,142
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
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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