Powrie F, Leach M W
DNAX Research Institute of Molecular and Cellular Biology Inc. Palo Alto, CA 93404, USA.
Ther Immunol. 1995 Apr;2(2):115-23.
A number of models of spontaneous chronic intestinal inflammation in mice and rats have recently been developed. A characteristic of the majority of these models is that disease developed as a consequence of immune manipulations, suggesting a central role for the immune system in the regulation of intestinal inflammation. Analysis of cytokine patterns in disease showed elevations in TNF-alpha and IFN-gamma, characteristic of the T-helper-1 (Th1) pathway, implicating Th1 cells and their cytokines in disease pathogenesis. Strikingly, inflammation did not develop in mice maintained in germ-free conditions, suggesting disease may develop due to a dysregulated inflammatory response to components of the normal flora. Evidence from a number of these models suggests that this potentially pathogenic inflammatory response does not develop in normal animals as it is actively inhibited by a population of CD4+ alpha beta + regulatory T cells and immunosuppressive cytokines such as IL-10 and TGF-beta 1. These new models will allow further investigation into the mechanisms of natural immune regulation and protection in the intestinal tract and how these mechanisms relate to the etiopathogenesis of inflammatory bowel disease (IBD). Furthermore, these models should provide useful insights for the design of effective immunomodulatory therapies for the treatment of IBD in humans.
最近已经开发出了许多小鼠和大鼠自发性慢性肠道炎症模型。这些模型中的大多数的一个特点是，疾病是免疫操纵的结果，这表明免疫系统在肠道炎症调节中起核心作用。对疾病中细胞因子模式的分析显示，肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）升高，这是辅助性T细胞1（Th1）途径的特征，表明Th1细胞及其细胞因子参与了疾病的发病机制。引人注目的是，在无菌条件下饲养的小鼠中不会发生炎症，这表明疾病可能是由于对正常菌群成分的炎症反应失调所致。来自许多这些模型的证据表明，这种潜在的致病性炎症反应在正常动物中不会发生，因为它受到一群CD4+αβ+调节性T细胞以及免疫抑制细胞因子（如白细胞介素-10（IL-10）和转化生长因子-β1（TGF-β1））的积极抑制。这些新模型将允许对肠道中天然免疫调节和保护机制以及这些机制与炎症性肠病（IBD）的病因发病机制之间的关系进行进一步研究。此外，这些模型应该为设计用于治疗人类IBD的有效免疫调节疗法提供有用的见解。
