Chlorpromazine inhibits concanavalin A-induced liver injury independently of cytokine modulation.
We investigated the effect of chlorpromazine (CPZ) in a murine model of T-cell-dependent liver injury caused by concanavalin A (ConA). CPZ (3 and 10 mg/kg) treatment 1 h before ConA injection prevented liver injury. CPZ (3, 10 mg/kg) administered 1 h after a ConA injection was also hepatoprotective, whereas cyclosporin (CsA, 100 mg/kg) was active only when given before ConA. Under either condition, CsA but not CPZ prevented concurrent increases in splenic ornithine decarboxylase (ODC) activity, a putative index of T-cell proliferation/differentiation. CPZ down-regulated tumor necrosis factor-alpha (TNF-alpha) and up-regulated IL-10 in mice that then received ConA, whereas delayed administration of CPZ had no effect. These results suggest that CPZ prevented liver injury without affecting the proliferation/differentiation of T-cells. The dissociation of hepatoprotection by CPZ from cytokine modulation indicates that this drug intervenes in the adherence of T-cells or the death of hepatocytes in the ConA-model.
Ikeda
K
K
Infectious Disease and Immunology Research Lab., Yamanouchi Pharmaceutical Co. Ltd, Ibaraki, Japan.
Hirano
M
M
Orita
A
A
Takeuchi
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D003208:Concanavalin A / Q000037:antagonists & inhibitors*; D016207:Cytokines / Q000097:blood / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000293:injuries; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009955:Ornithine Decarboxylase / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000201:enzymology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D003208:Concanavalin A; D009955:Ornithine Decarboxylase; D002746:Chlorpromazine