IL-10 suppresses experimental autoimmune neuritis and down-regulates T(H)1-type immune responses
IL-10 suppresses experimental autoimmune neuritis and down-regulates T(H)1-type immune responses
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DOI：
10.1006/clin.1997.4331
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发表时间：
1997-05-01
期刊：
影响因子：
--
通讯作者：
Link, H
中科院分区：
文献类型：
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作者：
Bai, XF;Zhu, J;Link, H
实验性自身免疫性神经炎（Experimental autoimmune neuritis，EAN）是一种由CD 4（+）T细胞介导的外周神经系统（peripheral nervous system，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IFN-gamma和TNF-alpha）与EAN的发病机制密切相关。白细胞介素10（IL-10）是一种T（H）2型细胞因子，可抑制单核细胞和T（H）1细胞的功能。我们检测了重组人IL-10（rHuIL-10）在EAN中的作用。当从免疫开始用乳化在弗氏完全佐剂中的牛外周髓磷脂给药时，IL-10有效地抑制和缩短临床EAN。即使在临床EAN建立后免疫后（pi）第12天后给予，IL-10也有效抑制EAN的严重程度。与对照EAN大鼠相比，IL-10处理的淋巴结中外周神经髓鞘抗原反应性IFN-γ分泌T（H）1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。与对照EAN大鼠相比，IL-10处理的P2蛋白反应性IFN-γ、TNF-α、IL-1 β和IL-6 mRNA表达淋巴结细胞在第14天和第26天也下调，而P2反应性IL-4 mRNA表达细胞在整个处理过程中上调。此外，在IL-10处理的EAN大鼠中，观察到上调的抗Pa IgG 1和下调的IgG 2a。我们的结果清楚地表明，rHuIL-10可以抑制临床EAN，并且这种抑制与T（H）1应答和巨噬细胞功能的下调以及T（H）2应答的上调有关。(C)1997年学术出版社。
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 T(H)2-type cytokine that suppresses monocyte and T(H)1 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 T(H)1-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-Pa 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 T(H)1 responses and macrophage function and upregulated T(H)2 responses. (C) 1997 Academic Press.