Role of 1,25-dihydroxyvitamin D3 in preventing acute rejection of allograft following rat orthotopic liver transplantation.
BACKGROUND
We investigated the role of 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) in preventing allograft from acute rejection following orthotopic liver transplantation.


METHODS
A rat orthotopic liver transplantation model was used in this study. SD-Wistar rats served as a high responder strain combination. Recipients were subjected to administration of 1,25-(OH)2D3 at dosages ranging from 0.25 microg.kg(-1).d(-1) to 2.5 microg.kg(-1).d(-1). Survival after transplantation as well as pathological rejection grades and IFN-gamma mRNA, IL-10 mRNA transcription intragraft on day 7, and day 30 post-transplantation were observed.


RESULTS
After recipients were treated with 1,25(OH)2D3 at dosages of 0.5 microg.kg(-1).d(-1) or 1.0 microg.kg(-1).d(-1), survivals of recipients were prolonged. Ninety-five percent confidence intervals of survival were 46 - 87 days and 69 - 102 days (both P = 0.0005 vs control group), respectively. On day seven post-transplantation, relative levels of IFN-gamma mRNA transcription were 0.59 +/- 0.12 and 0.49 +/- 0.16, which was higher than the control group (P = 0.005, P = 0.003, respectively). Relative levels of IL-10 mRNA transcription were 0.83 +/- 0.09 and 0.76 +/- 0.09, which was lower than the control group (P = 0.002, P = 0.003, respectively). At a dosage of 0.5 microg.kg(-1).d(-1), the median of pathological rejection grade on day seven and on day thirty post-transplantation were 1.5 and 2.0 in comparison with the CsA-treated group (P = 0.178, P = 0.171, respectively). At a dosage of 0.5 microg.kg(-1).d(-1), the median of pathological rejection grade on day seven and day thirty post-transplantation were 1.5 and 1.5 in comparison with CsA-treated group (P = 0.350, P = 0.693, respectively).


CONCLUSIONS
After each recipient was treated with 1,25-(OH)2D3 at a dosage of (0.5 - 1.0) microg.kg(-1).d(-1), transcription of cytokine intragraft was accommodated effectively and deviated to Th2 type, resulting in alleviation of acute rejection. 1,25-(OH)2D3 can prolong survival of recipient after orthotopic liver transplantation.
Zhang
Ai-bin
AB
Department of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital of College of Medicine, Zhejiang University and Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. cheung163 @163.com
Zheng
Shu-sen
SS
Jia
Chang-ku
CK
Wang
Yan
Y
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology / Q000502:physiology*; D006084:Graft Rejection / Q000517:prevention & control*; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014158:Transcription, Genetic
D016753:Interleukin-10; D007371:Interferon-gamma; D002117:Calcitriol