Effect of 1,25-dihydroxyvitamin D3 on preventing allograft from acute rejection following rat orthotopic liver transplantation.
OBJECTIVE
To study the mechanism and the preventive role of 1,25-dihydroxyvitamin D3 in acute rejection following orthotopic liver transplantation.


METHODS
Rats were randomly divided as donors or recipients for orthotopic liver allotransplantation model. Four groups were designed in the study, Group I: syngenic control (Wistar to Wistar); Group II: acute rejection (SD to Wistar); Group III: acute rejection treated with cyclosporine A, and Group IV: acute rejection treated with 1,25-(OH)2D3. Liver function, rejection activity index and mRNA of IFN-gamma, IL-10 in intragraft in recipients were measured in on day 1, 5, 7, 15, 30 posttransplant for assessing graft function, severity of acute rejection and immune state of recipients.


RESULTS
Survival time of recipients in Group VI was significantly prolonged (over 100 days) in comparison with other groups (vs Group II, P<0.001; vs Group III, P>0.05). After treatment with 1,25-(OH)2 D3, mean value of all the assay tested on each experimental time was compared, liver function in group IV was significantly improved (AST 127+/-41 U/L-360+/-104 U/L, BIL 13+/-5 mmol/l-38+/-11 mmol/l; vs Group II, P<0.05; vs Group III, P>0.05. Rejection activity index was significantly decreased (0-3.3+/-1.6; vs Group II, P<0.05; vs Group III, P>0.05). Level of hepatic IFN-gamma mRNA in group IV was decreased, while level of hepatic IL-10 mRNA was increased (vs Group II, P<0.05; vs Group III, P>0.05).


CONCLUSIONS
Our results indicated that 1,25-(OH)2D3 induced the secretion of cytokine toward to Th2 type, which would alleviate acute rejection, protect liver function and prolong survival of recipient after orthotopic liver transplantation.
Zhang
Ai-Bin
AB
Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of Medicine School, Zhejiang University, Hangzhou 310003, Zhejiang Province, China. cheung163@163.com
Zheng
Shu-Sen
SS
Jia
Chang-Ku
CK
Wang
Yan
Y
D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous
D000276:Adjuvants, Immunologic; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma; D002117:Calcitriol; D002118:Calcium