CYTOKINES AND AUTOIMMUNE BETA-CELL DESTRUCTION IN NOD MOUSE FETAL PANCREAS ISOGRAFTS IN CYCLOPHOSPHAMIDE-INDUCED DIABETES

The role of cytokines in a model of cyclophosphamide (CP)-accelerated beta cell destruction in fetal pancreas isografts transplanted into NO D mice was studied, One group of prediabetic NOD mice was injected wit h CP at a dose of 300 mg/kg ip and 7 days later isografts of organ cul tured fetal pancreas (FP) were transplanted under the kidney capsule o f these and untreated control mice. The mice were killed at several ti me points posttransplantation and the histological appearance of the h ost pancreas used to evaluate the disease progress in the grafts since previous studies had shown good corellation between isograft and nati ve pancreas pathology. Intragraft cytokine gene expression was monitor ed by reverse-transcriptase polymerase chain reaction (RT-PCR) at the same time points and the expression levels between the experimental gr oups compared to normal kidney tissue. In comparison to isografts from non-CP injected mice, isografts from CP-treated mice showed increased expression of IFN-gamma, TNF-alpha, TNF-beta, IL-5, and eotaxin but n o increase in IL-10 expression. The enhanced transcription of these cy tokines correlated with massive infiltration of immune cells and ongoi ng beta cell destruction in the host pancreas of the CP-treated recipi ents.