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Role of macrophages and macrophage-derived cytokines in the pathogenesis of Kilham rat virus-induced autoimmune diabetes in diabetes-resistant BioBreeding rats.

Authors
Chung, YH; Jun, HS; Kang, Y; Hirasawa, K; Lee, BR; Van Rooijen, N; Yoon, JW
Citation
Journal of immunology (Baltimore, Md. : 1950), 159(1):466-471, 1997
Journal Title
Journal of immunology (Baltimore, Md. : 1950)
ISSN
0022-17671550-6606
Abstract
The diabetes-resistant BioBreeding (DR-BB) rat, derived from diabetes-prone forebears, does not normally develop spontaneous insulitis or diabetes, but when infected with Kilham rat virus (KRV) this animal develops autoimmune diabetes similar to the diabetes-prone BioBreeding (DP-BB) rat. In this study, we attempted to determine whether macrophages and macrophage-derived cytokines play a role in the development of KRV-induced diabetes in DR-BB rats. Seventy-eight percent of DR-BB rats treated with KRV and poly(I:C) develop diabetes, whereas depletion of macrophages with liposome-encapsulated dichloromethylene diphosphonate (lip-Cl2MDP) in KRV and poly(I:C)-treated DR-BB rats results in the near-complete prevention of insulitis and diabetes. Measurement of the macrophage-derived cytokines IL-12, TNF-alpha, and IL-1beta revealed a selective increase of their expression, after KRV infection, in the splenic lymphocytes and the pancreatic islets. Measurement of CD4+ T cell-derived cytokines revealed that IL-2 and IFN-gamma cytokine gene expression closely correlates with an elevation of IL-12, but IL-4 and IL-10 do not change. Depletion of macrophages before the isolation of splenic lymphocytes from DR-BB rats treated with KRV and poly(I:C) resulted in the loss of ability to transfer diabetes to young DP-BB rats. On the basis of these observations, we conclude that macrophages and macrophage-derived cytokines play a critical role in the cascade of events leading to the destruction of pancreatic beta cells, culminating in the development of insulin-dependent diabetes mellitus.
MeSH terms
AnimalsBreedingCytokines/*immunologyDiabetes Mellitus, Type 1/genetics/*immunology/virologyMacrophage Activation/*immunologyMacrophages/*immunology*ParvovirusRats
PMID
9200487
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
AJOU Authors
강, 엽윤, 지원
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