The role of intravenous immunoglobulin therapy in mediating skin fibrosis in tight skin mice
The role of intravenous immunoglobulin therapy in mediating skin fibrosis in tight skin mice
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DOI：
10.1002/art.10363
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发表时间：
2002-06-01
影响因子：
--
通讯作者：
Shoenfeld, Y
中科院分区：
文献类型：
--
作者：
Blank, M;Levy, Y;Shoenfeld, Y
系统性硬化症（SSc）是一种自身免疫性结缔组织疾病，其特征是微血管损伤、细胞外基质沉积和纤维化。尽管该疾病的病因尚不清楚，但白细胞介素 4 (IL-4) 和转化生长因子 (TGF) 被认为在纤维形成中发挥着重要作用。已证明，IL-4 受体和 TGF 基因的突变可在动物模型中预防该疾病的发生 (1)。静脉注射人免疫球蛋白 (IVIG) 已成功用于对照临床试验，并且其治疗各种自身免疫性疾病的有效性已得到证实 (2)。此前，我们报道了 3 名 SSc 患者，通过客观皮肤评分测量，IVIG 治疗降低了皮肤纤维化程度 (3)。在本研究中，我们评估了 IVIG 对紧致皮肤 (Tsk/) 小鼠皮肤纤维化的影响。 Tsk/小鼠代表了硬皮病样疾病的鼠模型，其具有与人类硬皮病中所见的皮肤纤维化相似的遗传性纤维化。这些小鼠的过度纤维化是皮肤中胶原蛋白合成和积累增加的结果 (4)。 Tsk/小鼠 (n 5) 从 4 周龄开始接受 IVIG (Omrix, Nes-Ziona, Israel)。 IVIG 每周注射两次，持续 4 周。总剂量为2克/千克。对照小鼠 (n 5) 被注射 2% 麦芽糖。小鼠在9周龄时被处死。
Systemic sclerosis (SSc) is an autoimmune connective tissue disease that is characterized by microvascular damage, extracellular matrix deposition, and fibrosis. Although the cause of the disease is unknown, interleukin-4 (IL-4) and transforming growth factor (TGF) have been postulated to play a major role in the fibrogenesis. It has been demonstrated that mutation of the IL-4 receptor and TGF genes prevents the development of the disease in animal models (1). Intravenously administered human immunoglobulin (IVIG) has been used successfully in controlled clinical trials, and its effectiveness has been established, for the treatment of various autoimmune conditions (2). Previously, we reported on 3 patients with SSc in whom IVIG treatment reduced the degree of cutaneous fibrosis as measured by an objective skin score (3).In the present study, we assessed the effect of IVIG on skin fibrosis in tight skin (Tsk/) mice. The Tsk/mouse represents a murine model of scleroderma-like disease with heritable fibrosis resembling the skin fibrosis seen in human SSc. The excessive fibrosis in these mice is the result of increased synthesis and accumulation of collagen in the skin (4). Tsk/mice (n 5) received IVIG (Omrix, Nes-Ziona, Israel) beginning at the age of 4 weeks. IVIG was administered twice weekly for 4 weeks. The total dose was 2 gm/kg. Control mice (n 5) were infused with 2% maltose. The mice were killed at the age of 9 weeks.