Antiplatelet drug therapy moderates immune-mediated liver disease and inhibits viral clearance in mice infected with a replication-deficient adenovirus.
Treatment with a low dose of combined aspirin and clopidogrel, two antiplatelet drugs widely used in humans, markedly reduced the homing of virus-specific cytotoxic T lymphocytes and virus-nonspecific inflammatory leukocytes to the liver of mice acutely infected with a hepatotropic, replication-deficient, lacZ-expressing adenovirus (RAd35). Consequently, aspirin/clopidogrel-induced platelet dysfunction greatly diminished liver disease severity and inhibited viral clearance. Along with the finding that aspirin/clopidogrel caused neither bleeding nor anemia, our results suggest that antiplatelet drugs may be considered to limit excessive liver immunopathology and/or to facilitate the persistence of hepatotropic viral vectors utilized in gene therapy.
Iannacone
Matteo
M
Department of Molecular and Experimental Medicine, Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA.
Sitia
Giovanni
G
Narvaiza
Iñigo
I
Ruggeri
Zaverio M
ZM
Guidotti
Luca G
LG
D000256:Adenoviridae / Q000187:drug effects* / Q000502:physiology; D000257:Adenoviridae Infections / Q000188:drug therapy* / Q000821:virology; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology; D007154:Immune System Diseases / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D007962:Leukocytes / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008107:Liver Diseases / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin