Catholic University of Korea, Seoul, South Korea.
Arthritis Rheumatol. 2014 Jul;66(7):1768-78. doi: 10.1002/art.38627.
Intravenous immunoglobulin (IVIG) is used as a therapeutic agent in various autoimmune diseases. The aims of this study were to investigate the therapeutic effects of IVIG on collagen-induced arthritis (CIA) and identify the mechanism responsible for any therapeutic effects.
IVIG was administered to mice with CIA, and the in vivo effects were determined. Th17 and Treg cell frequencies were analyzed by flow cytometry, and cytokine levels in the supernatant were measured by enzyme-linked immunosorbent assay. Subpopulations of T cells and B cells in the spleen were assessed by confocal microscopy.
The arthritis severity score and incidence of arthritis were lower in mice treated with IVIG compared with untreated mice. Histopathologic analysis showed less joint damage in mice treated with IVIG. The expression of proinflammatory cytokines, specific type II collagen antibodies, and osteoclast markers was significantly reduced in mice treated with IVIG. Administration of IVIG induced increased FoxP3 expression and inhibited Th17 cell development. The number of FoxP3+ Treg cells was increased, and the number of Th17 cells was decreased in the spleens of mice treated with IVIG. The number of FoxP3+ follicular helper T cells was increased, and subsequent maturation of germinal center B cells was inhibited by IVIG. In addition, IVIG up-regulated interleukin-10 (IL-10) and Fcγ receptor IIB expression. The treatment effects of IVIG on arthritis were lost in IL-10-knockout mice.
These results showed that IVIG has therapeutic effects by modulating CD4+ T cell differentiation. The therapeutic effects of IVIG are dependent on IL-10.
静脉注射免疫球蛋白（IVIG）被用作各种自身免疫性疾病的治疗剂。本研究旨在探讨 IVIG 对胶原诱导性关节炎（CIA）的治疗作用，并确定其治疗作用的机制。
给 CIA 小鼠给予 IVIG，并通过流式细胞术分析体内效应，通过酶联免疫吸附试验测量上清液中的细胞因子水平。通过共聚焦显微镜评估脾中 T 细胞和 B 细胞的亚群。
与未治疗的小鼠相比，用 IVIG 治疗的关节炎小鼠的关节炎严重程度评分和关节炎发生率较低。组织病理学分析显示用 IVIG 治疗的小鼠关节损伤较少。用 IVIG 治疗可显著降低促炎细胞因子、特异性 II 型胶原抗体和破骨细胞标志物的表达。IVIG 给药诱导 FoxP3 表达增加并抑制 Th17 细胞发育。用 IVIG 治疗的小鼠脾脏中 FoxP3+Treg 细胞数量增加，Th17 细胞数量减少。FoxP3+滤泡辅助 T 细胞数量增加，IVIG 抑制生发中心 B 细胞的成熟。此外，IVIG 上调白细胞介素 10（IL-10）和 Fcγ 受体 IIB 的表达。IL-10 敲除小鼠的 IVIG 对关节炎的治疗作用丧失。
这些结果表明，IVIG 通过调节 CD4+T 细胞分化发挥治疗作用。IVIG 的治疗作用依赖于 IL-10。
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