细胞因子对体外培养的人球后成纤维细胞增殖及合成透明质酸、胶原蛋白的影响

Effect of interferon γ and interleukin 4 on proliferation and synthesis of hyaluronic acid and collagen in cultured human retroorbital fibroblasts in vitro

目的探讨甲状腺相关眼病（ＴＡＯ）的细胞免疫机制，并为临床上开展细胞因子或抗细胞因子疗法提供理论依据。方法采用Ｔｈ１细胞代表细胞因子干扰素（ＩＦＮ）γ和Ｔｈ２细胞代表细胞因子白细胞介素（ＩＬ）４，刺激体外培养的人球后成纤维细胞（ＲＦ），并用液体闪烁测量和放射自显影技术观察ＲＦ的增殖和合成透明质酸（ＨＡ）、Ⅳ型胶原蛋白的能力。结果ＩＦＮγ明显刺激ＲＦ增殖及合成ＨＡ，抑制其合成Ⅳ型胶原蛋白；ＩＬ４刺激ＲＦ增殖和合成Ⅳ型胶原蛋白，却抑制其合成ＨＡ；ＩＦＮγ（１００Ｕ／ｍｌ）和ＩＬ４（１μｇ／Ｌ）共同作用于ＲＦ时，可拮抗其各自对ＲＦ的刺激增殖作用，对ＨＡ和Ⅳ型胶原蛋白合成的刺激或抑制作用也得到中和。结论在ＴＡＯ发生发展中，ＩＦＮγ主要起炎症的致病作用，而ＩＬ４则对ＴＡＯ起修复和调节作用。

Objective To investigate the cellular immune mechanism of thyoid associated opthalmopathy (TAO) and provide a theory for treating TAO with cytokine or anti cytokine agents, it is essential to determine whether interferon (IFN) γ and interleukin (IL) 4, which are representative cytokines of Th1 and Th2 cells may have some effects on the developing and progressing of TAO. Methods Retroorbital fibroblasts (RF) proliferation and synthesis of hyaluronic acid(HA) and type Ⅳ collagen were measured with radioimmunoassay and radioauto graphy. Results IFN γ stimulated RF proliferation and HA synthesis and had significant inhibitory effect on type Ⅳcollagen synthesis. IL 4 stimulated proliferation and type Ⅳcollagen synthesis in RF and had inhibitory effect on HA synthesis. When IFN γ (100 U/ml) and IL 4 (1 μg/L)were incubated together with RF, they antagonized their stimulatory or inhibitory effect each other on proliferation and synthesis of HA and type Ⅳ collagen. Conclusion IFN γ, a representative cytokine of Th1 cells, was responsible for the inflammatory process of TAO, whereas IL 4, a representative cytokine of Th2 cells, had some effects on the repairing process. IL 4 could antagonized the inflammatory effect of IFN γ on RF.