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. 2013 Dec 19;7(12):e2599.
doi: 10.1371/journal.pntd.0002599. eCollection 2013.

The cytokine and chemokine profiles in patients with hand, foot and mouth disease of different severities in Shanghai, China, 2010

Mei Zeng  1 , Xiaoyan Zheng  2 , Ruicheng Wei  2 , Na Zhang  2 , Kai Zhu  2 , Bin Xu  2 , Chun-Hui Yang  2 , Chun-Fu Yang  2 , Chaoyang Deng  2 , Dongbo Pu  1 , Xiaohong Wang  1 , Ralf Altmeyer  2 , Qibin Leng  2
Affiliations

The cytokine and chemokine profiles in patients with hand, foot and mouth disease of different severities in Shanghai, China, 2010

Mei Zeng et al. PLoS Negl Trop Dis. .

Abstract

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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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The correlation between host biomarkers and disease prognosis.
Levels of CCL27 (A), CXCL1 (B), and soluble VCAM-1 (C) in serum samples obtained from control patients (Ctrl, n = 20) and HFMD patients with or without CNS complications (n = 20, respectively). The line represents the average value. (D) Plots of soluble VCAM-1 concentrations in sera of HFMD patients against their maximal fever temperatures. Numbers above square brackets indicate P values for the corresponding comparisons.
Figure 2
Figure 2. The effect of methylprednisolone (MP) treatment on serum levels of IL-17A.
(A) IL-17A levels in serum samples obtained from control (Ctrl, n = 20) and HFMD patients (HFMD, n = 40). (B) IL-17A levels in serum samples obtained from untreated (n = 27) or MP-treated HFMD patients (n = 13). (C) IL-17A levels in serum samples obtained from untreated (n = 7) or MP-treated CNS-complicated HFMD patients (n = 13). Numbers above square brackets indicate P values for the corresponding comparisons.
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Grants and funding

This work was supported by the National Basic Research Program of China [973 Program, grant number 2011CB504903], the National Natural Science Foundation of China (grants #81172807, #31270951, and #30972726), the Li Ka Shing Foundation, and the 100-Talent Program of CAS. QL is supported by the SA-SIBS Scholarship Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.