Effects of combined immune therapy on survival and Th1/Th2 cytokine balance in rat orthotopic liver transplantation.
BACKGROUND
The induction of immune tolerance and suppression of allograft rejection has become the focus in the study of liver transplantation. The effect of immune therapy with anti-CD40L mAb alone or in combination with cyclosporine A (CsA) on the recipient survival and Th1/Th2 cytokine profile was studied to elucidate its immunological mechanism and role in rat orthotopic liver transplantation.


METHODS
The model of rat orthotopic liver transplantation was established by modified Kamada's technique. Recipients were divided into group A (control group): SD-->SD; group B (group of rejection): SD-->Wistar without any treatment; group C: SD-->Wistar with CsA monotherapy from day 1 to day 5; and group D: SD-->Wistar with CsA from day 1 to day 5 and anti-CD40L mAb on day 0 and day 2. The survival of the recipients in all groups was observed and ELISA technique was used to detect the level of cytokines in peripheral blood on post-transplant day 7.


RESULTS
The survival period of recipients in groups A (> 60 days) and D (> 60 days) was significantly longer than that in group B (13.8 +/- 2.4 days). The serum levels of interleukin 2 (IL-2) and interferon gamma in group B were significantly higher than those in other groups; the level of tumor necrosis factor alpha was higher but not statistically significant. In contrast, the serum levels of IL-4 and IL-10 in group D were elevated more significantly than those in group B (P < 0.05).


CONCLUSIONS
Combined immune therapy can prolong the survival of allografts. Increased expression of Th2 cytokines, which is closely related to the induction of tolerance and suppression of rejection, is beneficial to the long-term survival of recipients and allografts.
Cao
Hui
H
Department of General Surgery, Renji Hospital, Jiao Tong University School of Medicine, Shanghai 200127, China.
Liu
Hua
H
Wu
Zhi-yong
ZY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D023201:CD40 Ligand / Q000037:antagonists & inhibitors*; D016572:Cyclosporine / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007166:Immunosuppressive Agents; D023201:CD40 Ligand; D016572:Cyclosporine