Bai X F, Zhu J, Zhang G X, Kaponides G, Höjeberg B, van der Meide P H, Link H
Division of Neurology, Karolinska, Institute, Huddinge University Hospital, Stockholm, Sweden.
Clin Immunol Immunopathol. 1997 May;83(2):117-26. doi: 10.1006/clin.1997.4331.
Experimental autoimmune neuritis (EAN) is a CD4+ T cell-mediated monophasic inflammatory disorder of the peripheral nervous system (PNS). Cellular mechanisms, including macrophage and T cell infiltration, and cytokines like IFN-gamma and TNF-alpha are intimately involved in the pathogenesis of EAN. Interleukin 10 (IL-10) is a TH2-type cytokine that suppresses monocyte and TH1 cell functions. We examined the effect of recombinant human IL-10 (rHuIL-10) in EAN. When administered from the start of immunization with bovine peripheral myelin emulsified in Freund's complete adjuvant, IL-10 effectively suppressed and shortened clinical EAN. Even when given after Day 12 post immunization (pi) after clinical EAN had been established, IL-10 also effectively suppressed the severity of EAN. Pheripheral nerve myelin antigen-reactive IFN-gamma-secreting TH1-like cells were decreased in lymph nodes from IL-10-treated compared to control EAN rats. PNS autoantigen-induced T cell proliferation and B cell responses were not affected. P2 protein-reactive IFN-gamma, TNF-alpha, IL-1 beta, and IL-6 mRNA-expressing lymph node cells were also downregulated in IL-10-treated compared to control EAN rats at Day 14 and 26 pi, while P2-reactive IL-4 mRNA-expressing cells were upregulated throughout treatment. Also, in IL-10-treated EAN rats, upregulated anti-P2 IgG1 and downregulated IgG2a were observed. Our results clearly show that rHuIL-10 can suppress clinical EAN, and this suppression is associated with downregulation of TH1 responses and macrophage function and upregulated TH2 responses.
实验性自身免疫性神经炎（EAN）是一种由CD4 + T细胞介导的外周神经系统（PNS）单相炎症性疾病。细胞机制，包括巨噬细胞和T细胞浸润，以及细胞因子如干扰素-γ和肿瘤坏死因子-α，都与EAN的发病机制密切相关。白细胞介素10（IL-10）是一种TH2型细胞因子，可抑制单核细胞和TH1细胞功能。我们研究了重组人IL-10（rHuIL-10）对EAN的影响。从用弗氏完全佐剂乳化的牛外周髓鞘免疫开始给药时，IL-10可有效抑制并缩短临床EAN病程。即使在免疫后第12天（pi）临床EAN已确立后给药，IL-10也能有效抑制EAN的严重程度。与对照EAN大鼠相比，IL-10处理的大鼠淋巴结中分泌外周神经髓鞘抗原反应性干扰素-γ的TH1样细胞减少。PNS自身抗原诱导的T细胞增殖和B细胞反应不受影响。在第14天和26天pi时，与对照EAN大鼠相比，IL-10处理的大鼠淋巴结中表达P2蛋白反应性干扰素-γ、肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6 mRNA的细胞也下调，而在整个治疗过程中表达P2反应性白细胞介素-4 mRNA的细胞上调。此外，在IL-10处理的EAN大鼠中，观察到抗P2 IgG1上调和IgG2a下调。我们的结果清楚地表明，rHuIL-10可以抑制临床EAN，这种抑制与TH1反应和巨噬细胞功能的下调以及TH2反应的上调有关。
