Protective effect of glucocorticoid-free immunosuppressive regimen in allogenic islet transplantation.
BACKGROUND
The most common complication after allogenic islet transplantation is rejection. This study was to evaluate the effect of anti-rejection of glucocorticoid-free immunosuppressive regimen on allogenic islet transplantation.


METHODS
Tacrolimus (FK506) + mycophenolate mofetil (MMF) and FK506 + MMF + prednisone (Pred) were administered respectively for 2 weeks to inhibit rejection after allogenic islet transplantation in rats, which were compared with the control group. The concentrations of blood glucose, insulin and C-peptide were determined dynamically in recipients and the sites of transplantation were observed morphologically.


RESULTS
As compared with the control group without immunosuppressive agents, FK506 +MMF and FK506 + MMF + Pred could prolong the survival time of grafts significantly. There were many morphologically intact islets in the liver of recipients 2 months after transplantation. Group FK506 + MMF kept normal levels of blood glucose, insulin and C-peptide beyond 60 days after transplantation. In contrast, group FK506 + MMF + Pred secreted less C-peptide (P<0.05) and maintained a higher level of blood glucose concentration (P<0.01) after the operation. There was no significant difference in insulin concentrations between the two groups. The level of blood glucose beyond the first 2 weeks after drug withdrawal in group FK506 + MMF + Pred decreased obviously (P<0.05), and the secretion of insulin and C-peptide increased. These results were compared with those the first 2 weeks after transplantation and the first 2 weeks after drug withdrawal.


CONCLUSIONS
Both regimens of FK506 + MMF and FK506 + MMF + Pred could provide effective immunosuppression. Moreover the combined glucocorticoid-free immunosuppressive strategy of low-dose FK506 and MMF could protect islet grafts in islet transplantation without diabetogenic side-effects.
Du
Cheng-You
CY
Department of Hepatobiliary Surgery & Liver Transplantation, First Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400016, China. duchengyou@126.com
Xu
Er-Kan
EK
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000517:prevention & control; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011355:Prodrugs / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous
D001786:Blood Glucose; D002096:C-Peptide; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D007328:Insulin; D011355:Prodrugs; D009173:Mycophenolic Acid; D016559:Tacrolimus