Effect of chemokine receptor antagonist on small intestine transplantation in rats

Jianjun YANG; Mengbin LI; Weizhong WANG; Jing FU

ABSTRACT

BACKGROUND:

Rejection is the main cause of the failure in small intestine transplantation. Cellular immunity mediated by chemotatic factor and the receptor plays an important role in acute rejection. We regard chemokine receptor as target site to design the treatment, which may provide reference for the immunotherapy in clinical small intestine transplantation.

OBJECTIVE:

To observe the effect of chemokine receptor antagonist, regulated upon activation, normal T cell expressed and secreted (Met-RANTES), on the survival time and histopathological changes of allograft rats which have received heterotopic small intestine transplantation, and the coordinative effects of Met-RANTES used together with low-dose tacrolimus.DESIGN, TIME AND

SETTING:

Randomized complete-block design and controlled animal experiment, performed in the Department of Gastrointestinal Surgery, Xijing Hospital, the Fourth Military Medical University of Chinese PLA between September 2003 and March 2005.MATERIALS 180 healthy adult male rats including 90 rats (donors) and 90 Wistar rats (recipients) were involved in this study. Heterotopic segmental small intestine transplantation was performed.

METHODS:

The rats were randomly divided into 3 groups with 30 rats for each group. Control group Rats were treated with heterotopic small intestine transplantation alone; Met-RANTES group Rats were treated with an intraperitoneal injection of Met-RANTES (200 μg/d) at 0-7 days after transplantation; Met-RANTES+low-dose FK506 group Rats were treated with an intraperitoneal injection of Met-RANTES (200 μg/d)+tacrolimus (0.5 mg/kg/d) at 0-7 days after transplantation.MAIN OUTCOME

MEASURES:

Gross status and survival time were detected; in addition, every 6 rats were sacrificed at different time points, such as 1,3, 5, and 7 days after transplantation, to compare histopathological changes.

RESULTS:

Following transplantation, 90 Wistar rats (recipients) were all involved in the final analysis. The survival time median in the control group was 7.2 days (1.5), and all rats died of acute rejection and infection. Histopathological examination showed that mild, moderate and severe rejections were detected at day 3, 5, and 7 after transplantation, respectively. The survival time median in the Met-RANTES group was 19.2 days (16.4), which was significantly longer than the control group (P<0.01). The survival time median in the Met-RANTES+low-dose tacrolimus group was 30.9 days (9.0), and there were significant differences in survival rate as compared with control group and Met-RANTES group (P<0.01). While the rats in the Met-RANTES group and the Met-RANTES+low-dose tacrolimus group showed no obvious indication of rejection.

CONCLUSION:

Met-RANTES may obviously inhibit acute rejection following small intestine transplantation, effectively protect the function of grafts, and significantly prolong the survival time of the recipients. In addition, Met-RANTES may enhance the immunosuppressive function of low-dose tacrolimus.