Kolb H, Wörz-Pagenstert U, Kleemann R, Rothe H, Rowsell P, Rastegar S, Scott F W
Diabetes Research Institute at the University of Düsseldorf, Germany.
Autoimmunity. 1997;26(1):1-6. doi: 10.3109/08916939709009544.
Subcutaneous insulin treatment of young diabetes prone BB rats has been shown previously to suppress the development of autoimmune diabetes. In this study the hypothesis was tested that exogenous insulin may deviate the autoimmune process by acting on the Th1/Th2 cytokine balance in the pancreas. BB rats were implanted with pellets which continuously released insulin, at 50 d of age. Three weeks later cytokine mRNA expression in the pancreas and insulitis score were determined. While in control BB rats high levels of IFNgamma mRNA were detectable by RT-PCR, insulin treatment almost completely suppressed IFNgamma mRNA levels without concomitant upregulation of counterregulatory IL-10 and TGFbeta gene expression. Insulin also suppressed gene expression of inducible nitric oxide synthase. Mean insulitis scores were decreased after insulin treatment. We conclude that the protective effects of insulin treatment may not be due to the induction of protective Th2 immune reactivity but to general downregulation of immune activation in the pancreas, and hence also of Th1 autoimmunity.
先前已表明，对易患糖尿病的幼年BB大鼠进行皮下胰岛素治疗可抑制自身免疫性糖尿病的发展。在本研究中，对“外源性胰岛素可能通过作用于胰腺中的Th1/Th2细胞因子平衡来使自身免疫过程发生偏差”这一假说进行了验证。在50日龄时，给BB大鼠植入能持续释放胰岛素的微丸。三周后，测定胰腺中细胞因子mRNA表达及胰岛炎评分。通过逆转录聚合酶链反应（RT-PCR），在对照BB大鼠中可检测到高水平的γ干扰素（IFNγ）mRNA，而胰岛素治疗几乎完全抑制了IFNγ mRNA水平，同时并未伴随起反调节作用的白细胞介素-10（IL-10）和转化生长因子β（TGFβ）基因表达的上调。胰岛素还抑制了诱导型一氧化氮合酶的基因表达。胰岛素治疗后，平均胰岛炎评分降低。我们得出结论，胰岛素治疗的保护作用可能并非归因于诱导保护性Th2免疫反应性，而是由于胰腺中免疫激活的总体下调，因此也是Th1自身免疫的下调。
