Abstracts
1998 Digestive Disease Week

#1030

TREATMENT WITH ANTI-INTERLEUKIN-12 MONOCLONAL ANTIBODY ALLEVIATES ACUTE REJECTION OF MOUSE ISLET ALLOGRAFTS. Y.Wada, K.Arai, M. Sunamura, M.Kobari, and S.Matsuno. First Dept of Surgery, Tohoku University School of Medicine, Sendai, Japan.

Background&Purpose Interleukin (IL)-12 is a potent cytokine to promote Th1-mediated immune response. However, the role of IL-12 in the acute allograft rejection is still unclear. We examined the role of IL-12 in the acute rejection of murine islet allografts by use of rat anti-mouse IL-12 monoclonal antibody (C17.8).

Materials&Methods Six hundred islets from ICR mice were transplanted under the left renal capsule of streptozotocin-induced diabetic C57BL/6 mice. Islet transplanted mice received intraperitoneal administration of C17.8 (500 or 250 µ g) on days 0, 4, 8 and 12 after transplantation. Control group received islet transplantation without concomitant immunosuppression. 1) Graft survivals of each group were compared with mean survival time (MST) and histological studies. 2) Intragraft cytokine mRNA expression was assessed by RT-PCR. 3) IFN-_ in the culture supernatants of in vivo sensitized whole splenocytes which were restimulated with anti-CD3 antibody in vitro was assessed by ELISA to determine the systemic influence of C17.8 mAb.

Results 1) The MSTs of control group, 250 µg C17.8 mAb-treated group, and 500 µg mAb-treated group were 10.2 days, 15.2 days* and 30.8 days**, respectively. Significant prologation of graft survival was induced with C17.8 mAb treatment (*p<0.05 vs.control,** p<0.001 vs.control). 2) In control group, Th1 cytokine (IL-2, IFN- _) transcripts were dominant. In 500 µg mAbtreated group, Th1 cytokine gene expression were suppressed, while IL-10 expression on day 4 was detectable. 3) The production of IFN-_ in 500 µg mAb-treated group was decreased to half of that in control group on day 8 post-transplant.

Conclusion Post-transplant systemic administration of anti-IL-12 mAb may be useful to alleviate islet allograft rejection by blockade of Th1-mediated response through suppressed IFN-_ production. Thus, IL-12 may play a important role in islet allograft rejection.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.