Sa Eun-Ho, Jin Un-Ho, Kim Dong-Soo, Kang Bong-Seok, Ha Ki-Tae, Kim June-Ki, Park Won-Hwan, Kim Cheorl-Ho
Department of Biological Science, Sungkyunkwan University, Suwon City, Kyunggi-Do 440-746, Republic of Korea.
J Ethnopharmacol. 2007 Feb 12;109(3):472-9. doi: 10.1016/j.jep.2006.08.017. Epub 2006 Aug 26.
The crude herbal formulation, Gamgungtang (GGT), has been shown to protect animals against a wide range of spontaneously developing or induced autoimmune diseases. We have previously reported that GGT shows marked down-regulation of several experimental autoimmune diseases. Although very effective at preventing thyroid infiltrates in mice immunized with mouse deglycosylated thyroglobulin and complete Freund's adjuvant and in spontaneous models of thyroiditis, it completely failed to modify experimental autoimmune thyroiditis (EAT) induced in mice immunized with mouse thyroglobulin and lipopolysaccharide. In this study, in an effort to elucidate the mechanisms by which GGT suppresses EAT, and autoimmunity in general, we investigated the in vivo effects of this drug on the Th1/Th2 lymphocyte balance, which is important for the induction or inhibition of autoreactivity. Naive SJL/J mice were treated orally for 5 days with GGT (80 mg/(kg day)). Spleen cells were obtained at various time points during the treatment period and were stimulated in vitro with concanavalin A. Interleukins IL-4, IL-10 and IL-12, transforming growth factor-beta (TGF-beta) and interferon-gamma (IFN-gamma) cytokine production was evaluated at the protein levels of the cytokines in the medium and mRNA expressions. A significant upregulation of IL-4, IL-10 and TGF-beta was observed following treatment with GGT, which peaked at day 5 (IL-10) or day 10 (IL-4). On the other hand, IL-12 and IFN-gamma production were either unchanged or decreased. It seems therefore that GGT induces in vivo a shift towards Th2 lymphocytes which may be one of the mechanisms of down-regulation of the autoimmune reactivity in EAT. Our observations indicate that down-regulation of TH1 cytokines (especially IL-12) and enhancement of Th2 cytokine production may play an important role in the control of T-cell-mediated autoimmunity. These data may contribute to the design of new immunomodulating treatments for a group of autoimmune diseases.
粗制草药配方“加味肾气汤”（GGT）已被证明可保护动物免受多种自发发生或诱导产生的自身免疫性疾病的侵害。我们之前报道过，GGT对几种实验性自身免疫性疾病有显著的下调作用。尽管在预防用去糖基化小鼠甲状腺球蛋白和完全弗氏佐剂免疫的小鼠以及甲状腺炎自发模型中的甲状腺浸润方面非常有效，但它完全无法改变用小鼠甲状腺球蛋白和脂多糖免疫的小鼠所诱导的实验性自身免疫性甲状腺炎（EAT）。在本研究中，为了阐明GGT抑制EAT以及一般自身免疫的机制，我们研究了该药物对Th1/Th2淋巴细胞平衡的体内影响，这对自身反应性的诱导或抑制很重要。将未接触过抗原的SJL/J小鼠用GGT（80毫克/（千克·天））口服治疗5天。在治疗期间的不同时间点获取脾细胞，并在体外用刀豆球蛋白A刺激。在培养基中细胞因子的蛋白质水平和mRNA表达水平上评估白细胞介素IL-4、IL-10和IL-12、转化生长因子-β（TGF-β）和干扰素-γ（IFN-γ）细胞因子的产生。用GGT治疗后观察到IL-4、IL-10和TGF-β有显著上调，在第5天（IL-10）或第10天（IL-4）达到峰值。另一方面，IL-12和IFN-γ的产生要么没有变化，要么减少。因此，似乎GGT在体内诱导向Th2淋巴细胞的转变这可能是EAT中自身免疫反应下调的机制之一。我们的观察结果表明，Th1细胞因子（尤其是IL-12）的下调和Th2细胞因子产生的增强可能在控制T细胞介导的自身免疫中起重要作用。这些数据可能有助于为一组自身免疫性疾病设计新的免疫调节治疗方法。
