Cytokines and autoimmune β 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 NOD mice was studied. One group of prediabetic NOD mice was injected with CP at a dose of 300 mg/kg i.p. and 7 days later isografts of organ cultured fetal pancre...

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Bibliographic Details
Published in:Autoimmunity (Chur, Switzerland) Switzerland), 1997-01, Vol.26 (4), p.245-252
Main Authors: KOVARIK, J, FAULKNER-JONES, B. E, KOULMANDA, M, MANDEL, T. E
Format: Article
Language:English
Subjects:
Animals
Autoimmunity - immunology
Biological and medical sciences
Blood Glucose
Cyclophosphamide
Cytokines - genetics
Diabetes Mellitus, Type 1 - immunology
Experimental and animal immunopathology. Animal models
Female
Fetal Tissue Transplantation - immunology
Gene Expression
Immunopathology
Islets of Langerhans - immunology
Medical sciences
Mice
Mice, Inbred NOD
Pancreas - embryology
Pancreas - immunology
Pancreas - pathology
Pancreas Transplantation - immunology
Transplantation, Isogeneic
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Summary:The role of cytokines in a model of cyclophosphamide (CP)-accelerated beta cell destruction in fetal pancreas isografts transplanted into NOD mice was studied. One group of prediabetic NOD mice was injected with CP at a dose of 300 mg/kg i.p. and 7 days later isografts of organ cultured fetal pancreas (FP) were transplanted under the kidney capsule of these and untreated control mice. The mice were killed at several time points post-transplantation and the histological appearance of the host pancreas used to evaluate the disease progress in the grafts since previous studies had shown good correlation between isograft and native pancreas pathology. Intragraft cytokine gene expression was monitored by reverse-transcriptase polymerase chain reaction (RT-PCR) at the same time points and the expression levels between the experimental groups 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 no increase in IL-10 expression. The enhanced transcription of these cytokines correlated with massive infiltration of immune cells and ongoing beta cell destruction in the host pancreas of the CP-treated recipients.
ISSN:0891-6934
1607-842X
DOI:10.3109/08916939709008030