Inflammatory cytokine profiles of serum and cerebrospinal fluid in Chinese children with hand, foot and mouth disease.

OBJECTIVE

Hand, foot and mouth disease (HFMD) is mainly caused by enterovirus 71 (EV71) or coxsackie virus A16 infection. Severe HFMD with encephalitis is a life-threatening disease for children. This study aimed to examine the levels of a variety of inflammatory cytokines in HFMD patients.

METHODS

Sera of severe or common HFMD patients and cerebrospinal fluids from severe HFMD patients in the acute or recovery phase were collected to analyse 40 cytokines using the Raybiotec Cytokine array. Twenty-six samples of sera or cerebrospinal fluids from HFMD patients were further detected using Milliplex beads.

RESULTS

Numerous inflammatory cytokines, such as IL-8, IP-10, and RAENTES, were enhanced in the sera and cerebrospinal fluids of encephalitis-complicated HFMD patients. Serum IL-12p40 and IL-15 levels were higher in severe HFMD patients compared with common patients. Moreover, IL-8 and IP-10 levels in the cerebrospinal fluid were sharply enhanced by 30-fold on average compared with those in the sera. Cerebrospinal fluid IL-8, IP-10, and RANTES levels were significantly enhanced in the acute phase of severe HFMD patients compared with those in the recovery phase. However, no correlation of serum IL-8 or IP-10 level with its cerebrospinal fluid level was observed.

CONCLUSION

An inflammatory cytokine storm occurs both in sera and cerebrospinal fluids during severe HFMD, which is likely a Th1 cell-associated disease. Cerebrospinal fluid IL-8, IP-10 and RANTES levels could be used as potential biomarkers for diagnosing severe HFMD, whereas the enhanced serum levels of IL-12p40 and IL-15 could be used as candidate predictive factors for severe HFMD.