Rapamycin prevents concanavalin A-induced liver injury by inhibiting lymphocyte activation.
OBJECTIVE
Liver injury induced by concanavalin A (Con A) is often used as a model to study the pathophysiology of immune mediated liver injury. Rapamycin (Rapa) is an effective immunosuppressant widely used for preventing immune activation and transplant rejection. However, the effect of Rapa on liver injury caused by Con A has not been carefully examined. In the present study, we examined the effect of Rapa on liver injury caused by Con A.


METHODS
Mice received intraperitoneal Rapa injection before Con A intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the level of cytokines was detected by enzyme linked immunosorbent assay (ELISA).


RESULTS
In the present study, we examined the effect of Rapa on liver injury after Con A injection in mice. We found that the treatment of mice with Rapa protected the liver from Con A-induced injury. Pretreatment with Rapa dramatically ameliorated Con A-induced mortality. This protection was associated with reduced transaminase levels in the blood and further confirmed by liver histology. ELISA showed that Rapa suppressed pro-inflammatory cytokines IFN-gamma and TNF-alpha production as compared with the untreated controls. Furthermore, intrahepatic lymphocyte proliferation was significantly inhibited.


CONCLUSIONS
These findings suggested that Rapa has the therapeutic potential for treatment of immune-mediated liver injury in the clinic.
Zhang
Yuanqing
Y
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
Xiao
Xiang
X
Li
Xianchang
X
Wei
Haiming
H
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D003208:Concanavalin A; D019610:Cytoprotection; D004195:Disease Models, Animal; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma; D000637:Transaminases; D020123:Sirolimus