Jiang Z, Woda B A
Department of Pathology, University of Massachusetts Medical Center, Worcester 01655.
J Immunol. 1991 May 1;146(9):2990-4.
The Biobreeding Worcester rat provides one of the best models of autoimmune diabetes. Immunopathologic studies of acute diabetes show that the islets are infiltrated by T cells and macrophages. It has been hypothesized that the islets are damaged by the secretion of cytokines such as IL-1 and TNF-alpha and that their function may be altered by IL-6. In this study, we utilized in situ hybridization to determine the expression of the IL-1, TNF, and IL-6 genes within the pancreas of the acute diabetic Biobreeding Worcester rat. These studies showed that cells expressing IL-1, TNF, and IL-6 were present within the islets and in the exocrine pancreas surrounding islets, ducts, and vessels and in an interstitial location. Cells expressing TNF and IL-1 mRNA were present in about 20% of the islets, whereas cells expressing IL-6 were present in about 4% of the islets. Islets containing TNF- or IL-1-positive cells contained about three positive cells per islet whereas only about one IL-6-positive cell was present per islet. In 26% of the islets peri-insular TNF-positive cells were found. Peri-insular IL-1 positive cells were seen in 14% of the islets and 8% showed peri-insular IL-6 positive cells. In nondiabetic 30-day old DP or 90-day-old DR rats intra-islet cytokine gene expression was not seen. Our studies support the view that cytokines are important in beta cell destruction.
BioBreeding伍斯特大鼠是自身免疫性糖尿病的最佳模型之一。急性糖尿病的免疫病理学研究表明，胰岛被T细胞和巨噬细胞浸润。据推测，胰岛会因白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）等细胞因子的分泌而受损，并且其功能可能会被IL-6改变。在本研究中，我们利用原位杂交技术来确定急性糖尿病BioBreeding伍斯特大鼠胰腺中IL-1、TNF和IL-6基因的表达情况。这些研究表明，表达IL-1、TNF和IL-6的细胞存在于胰岛内、胰岛周围的外分泌胰腺中、导管和血管中以及间质位置。表达TNF和IL-1 mRNA的细胞存在于约20%的胰岛中，而表达IL-6的细胞存在于约4%的胰岛中。含有TNF或IL-1阳性细胞的胰岛每个胰岛约有三个阳性细胞，而每个胰岛仅约有一个IL-6阳性细胞。在26%的胰岛中发现了岛周TNF阳性细胞。在14%的胰岛中可见岛周IL-1阳性细胞，8%的胰岛显示有岛周IL-6阳性细胞。在30日龄的非糖尿病DP大鼠或90日龄的DR大鼠中未观察到胰岛内细胞因子基因表达。我们的研究支持细胞因子在β细胞破坏中起重要作用这一观点。
