Wu Z, Holwill S D J, Oliveira D B G
Department of Cellular and Molecular Medicine, St George's Hospital Medical School, London, UK.
Clin Exp Immunol. 2004 Feb;135(2):194-9. doi: 10.1111/j.1365-2249.2003.02372.x.
A rise in interleukin (IL) 4-dependent immunoglobulin E (IgE) is a hallmark of the mercuric chloride (HgCl2)-induced Th2-mediated autoimmune syndrome in the Brown Norway (BN) rat, and one of the mediators in allergic asthma in human. Oxidative stress, a potential factor related to the pathogenesis of allergy and asthma, has been shown to up-regulate IL-4 in mast cells and predispose to degranulation in vitro. However, it remains unknown whether oxidative/antioxidative imbalance plays a role in this Th2-driven model of autoimmunity in the rat. Here we show that administration of the non-sulphydryl-containing antioxidant desferrioxamine i.p. and s.c. to BN rats reduces HgCl2-enhanced IL-4 gene expression and inhibits HgCl2-induced Th2-mediated autoimmunity. Desferrioxamine treatment suppresses significantly IgE production and lymphoproliferation, and reduces tissue injury in the form of caecal vasculitis in the HgCl2-induced autoimmune syndrome. These results support a role for oxidative stress in the pathogenesis of the HgCl2-induced Th2-dominated autoimmune syndrome. This finding might have implications for understanding the mechanisms involved in Th2 cell responses as seen in allergy and asthma and thereby aid the development of new therapeutic strategies for these diseases.
白细胞介素（IL）-4依赖性免疫球蛋白E（IgE）升高是氯化汞（HgCl₂）诱导的棕色挪威（BN）大鼠Th2介导的自身免疫综合征的一个标志，也是人类过敏性哮喘的介质之一。氧化应激是与过敏和哮喘发病机制相关的一个潜在因素，已被证明可上调肥大细胞中的IL-4，并在体外易引发脱颗粒。然而，氧化/抗氧化失衡是否在大鼠这种Th2驱动的自身免疫模型中起作用仍不清楚。在此我们表明，对BN大鼠腹腔注射和皮下注射不含巯基的抗氧化剂去铁胺，可降低HgCl₂增强的IL-4基因表达，并抑制HgCl₂诱导的Th2介导的自身免疫。去铁胺治疗可显著抑制IgE产生和淋巴细胞增殖，并减轻HgCl₂诱导的自身免疫综合征中盲肠血管炎形式的组织损伤。这些结果支持氧化应激在HgCl₂诱导的以Th2为主的自身免疫综合征发病机制中的作用。这一发现可能有助于理解在过敏和哮喘中所见的Th2细胞反应所涉及的机制，从而有助于开发针对这些疾病的新治疗策略。
