類風濕性關節炎是一種慢性發炎性疾病，主要是Th1 (T helper 1)細胞的自體免疫功能失調所引起的。此種疾病的特徵為免疫細胞和活化的滑液膜細胞浸潤於關節腔中，導致發炎反應產生並伴隨著進展性的軟骨和硬骨的侵蝕與破壞。細胞激素介白素10 一直以來被認為具有潛在抗發炎和抑制免疫反應的特性，這是由於它可抑制先天性免疫細胞的許多功能包括抗原呈獻和發炎性細胞激素的釋放。介白素19 是介白素10 的轉錄活化因子，在過去的文獻指出，其有能力去誘導下游介白素10 的產生。除此之外，介白素19 還可影響T 細胞的成熟，改變Th1/Th2 的平衡，使之偏向於Th2 的反應。而此篇研究的主要目的是在研究介白素19 基因的給予對於實驗性關節炎的小鼠是否具有治療的效果。我們首先利用DBA/1J 小鼠建立了一個膠原蛋白誘發關節炎 (collagen-induced arthritis, CIA)的小鼠動物模式，模擬人類上的類風濕性關節炎。接著我們構築帶有小鼠介白素19 基因之慢病毒，命名為Lv.mIL19，利用Lv.mIL-19 感染細胞探討介白素19 的生物功能。此外，更進一步地評估Lv.mIL19 和病毒控制組Lv.GFP 全身性地給予CIA 的DBA/1J 小鼠動物模式之影響。與Lv.GFP 和saline 組比較起來，我們發現在Lv.mIL19 治療之CIA 小鼠，其關節炎的臨床症狀、關節指數 (articular index)與組織病理學 (histological appearance)都有改善的情況。這些發現提供了實驗上的證據已便未來利用慢病毒載體攜帶介白素19 基因以治療人類的類風濕性關節炎或甚至其他的發炎性疾病，並提供了介白素19 也許可用來治療類風濕性關節炎的新觀念。

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with a dominant Th1 (T helper 1) phenotype. In the case of RA, the synovium is highly infiltrated by immune cells and activated of synovial cells, leading to joint inflammation as well as progressive cartilage and bone erosion. Interleukin (IL)-10 exerts potent anti-inflammatory and immunosuppressive properties, which contribute to its ability to inhibit several functions of innate immune cells, including antigen presentation and proinflammatory cytokine production. IL-19 is a transcriptional activator of IL-10, which potently induces IL-10 production. Furthermore, IL-19 can alter the balance
of Th1/Th2 cells in favor of Th2. The aim of this study was to investigate the therapeutic effects of IL-19 gene transfer on experimental arthritis in mice. We first established a mouse model of collagen-induced arthritis (CIA) in DBA/1 mice that mimics human RA. We constructed a lentiviral vector encoding mouse IL-19, designated Lv.mIL-19. The characterization and bioactivity of IL-19 expressed by Lv.mIL-19 were validated in vitro. Furthermore, Lv.mIL-19 and Lv.GFP were injected systemically to DBA/1 mice that had been immunized with bovine type II collagen, and their treatment responses were monitored. Compared with Lv.GFP or saline treatment, Lv.mIL-19 treatment reduced articular index and histological appearance of the mice with CIA. Taken together, these findings provide experimental evidence for the feasibility of lentivirus-mediated IL-19 gene transfer for the amelioration of RA or other inflammatory diseases. In addition, this study also supports the concept that IL-19 may be a new therapeutics for the treatment of RA.

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