12月19日，国际学术期刊PLOS Neglected Tropical Diseases在线发表了中科院上海巴斯德研究所的研究论文The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai, China, 2010。

　　手足口病是一种由肠道病毒71型、柯萨奇病毒A16等多种肠道病毒引起的传染性疾病，主要发病于5岁以下儿童。近年来, 手足口病在亚洲地区多次暴发流行，已成为严重的公共健康隐患。系统性促炎症细胞因子的上调是并发肺水肿的危重症手足口病患者的一个重要特征。免疫调节药物，如类固醇药物，已经在我国广泛应用于治疗包括没有肺水肿症状的重症手足口病，但到目前为止，仍无法确定在不同严重程度的手足口病中，类固醇药物是否能够有效地抑制炎症。

　　上海巴斯德所冷启彬课题组、艾德铭课题组和复旦大学附属儿科医院进行合作，系统性地分析了不同严重程度患者的血清中炎症细胞因子、趋化因子、生长因子以及可溶性免疫受体的表达水平。检测结果发现，相对于非感染性疾病患者，不同严重程度的手足口病患者都具有很高的炎症反应，其中14种生物因子如IL-6、IFN-γ等的表达量显著性上调；同时伴随12种因子如IL-1Ra、IL-8等表达量显著性下调，并发现血管细胞粘附因子-1的表达水平同患者发烧体温高低有显著相关性；说明即便是非危重症手足口病患者也具有上调的系统性炎症反应。

   然而，用类固醇药物甲泼尼龙治疗过后，患者血清中手足口病标志性炎症因子的表达水平与没有接受治疗的患者并没有太大的区别，却增加了促神经性炎症因子IL-17A的产生。该研究结果表明，类固醇药物治疗对于手足口病引起的患者系统性炎症反应没有显著作用，其疗效有待于进一步深入研究。

    此项研究获得了国家自然科学基金、国家重大科学研究计划（973）和李嘉诚基金的资助。

原文摘要：

The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai
BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients.

METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone.

RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD.

CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.

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