Cytokine regulationin keratinocyte and fibroblast-the role in allegic disense-

特应性皮炎(AD)患者有时合并哮喘或鼻炎，提示存在全身性变态反应性疾病。为了研究AD患者的腹部症状和结肠疾病，我们研究了31例成人重症AD患者。31例患者中有22例显示为结肠炎。组织学上，所有患者都有结肠炎的证据，其特征是明显的嗜酸性粒细胞浸润。AD和结肠炎患者外周血嗜酸性粒细胞增多，血清LDH和IgE水平升高。定量RT-PCR显示AD相关性结肠炎患者的结肠和皮肤活检组织中的TNFpha mRNA表达水平高于对照组。我们通过检测炎性细胞因子刺激表皮角质形成细胞(KC)对嗜酸性粒细胞趋化因子产生的影响，探讨了特应性皮炎患者嗜酸性粒细胞趋化的机制。同时进行…培养的角质形成细胞在更多的干扰素和肿瘤坏死因子的作用下，趋化嗜酸性粒细胞的能力增强，RANTES基因和蛋白的表达水平增强。我们的结果表明，角质形成细胞产生RANTES可能有助于解释特应性皮炎中嗜酸性粒细胞渗入皮肤的原因。我们比较了生物反应调节剂(BRM)对BMT皮损形成的影响。5例接受BMT的患者静脉注射GM-CSF后，2例患者出现特应性皮炎样皮损，毛囊周围有中性粒细胞、嗜酸性粒细胞和淋巴细胞浸润，其他器官没有GVHD的其他征象。未接受BRM治疗的患者中无一例发生急性移植物抗宿主病(AGVHD)。我们的数据表明，严重的AD与结肠炎的高患病率有关，结肠炎在病因上可能是过敏的。在过敏性皮肤病中，如特应性皮炎，嗜酸性粒细胞从血液循环迁移到皮肤。这些结果表明，多种细胞因子(RANTES、TNFα、GM-CSF)来源于皮肤嗜酸性粒细胞，在AD发病中起重要作用。较少

Patients with atopic dermatitis (AD) sometimes have intercurrent asthma or rhinitis, suggesting the presence of generalized allergic disease. To investigate abdominal symptoms and colonic disorders in patients with AD,we studied 31 adult patients with severe AD.Twenty-two of 31 patients exhibited endoscopic evidence of colitis. Histologically, all patients had evidence of colitis characterized by a marked eosinophilic infiltration. Peripheral eosinophilia and high serum LDH and IgE levels were present in patients with AD and colitis. Quantitative RT-PCR of TNFalpha revealed high expression of TNFalpha mRNA in colonic and skin biopsy specimens from patients with AD-associated colitis compared to control patients. We investigated the mechanisms of eosinophil chemotaxis in atopic dermatits by examining the effect of stimulation of epidermal keratinocytes (KC) by inflammatory cytokines, IFN-_<gamma> and / or TNF-_<alpha>, on the production of eosinophils chemotactic factors. Simultaneous a … More ddition of IFN-_<gamma> and TNF-_<alpha> to cultured keratinocytes synergistically increased eosinophils chemotaxis and the expression of RANTES mRNA and protein level on these cells. Our results indicate that the production of RANTES by keratinocytes may help to explain eosinophil infiltration into the skin in atopic dermatitis. We compared the effect of biological response modifiers (BRM) on development of skin lesions, in BMT.Administration of GM-CSF intravenously in five patients who received BMT resulted in atopic-dermatitis-like lesions in two patients with infiltration of neutrophils, eosinophils and lymphocytes around the follicle, without other signs of GVHD in other organ. None of the patients who were not treated with BRM developed acute GVHD (aGVHD). Our data suggest that severe AD is associated with a high prevalence of colitis which may be allergic in etiology. In allergic skin diseases such as atopic dermatitis, eosinophils migrate from the circulation to the skin. These results showed that several cytokines (RANTES,TNFalpha, GM-CSF) from skin eosinophils and pay an important role for AD. Less