Serum interleukin-6 levels as an indicator of aseptic meningitis among children with enterovirus 71-induced hand, foot and mouth disease

ABSTRACT

Objectives: The enterovirus EV71 is a major pathogen of hand, foot, and mouth disease (HFMD) in children. Aseptic meningitis is the most common neurologic complication of EV71-induced HFMD. Lumbar puncture is a crucial procedure in the diagnosis of aseptic meningitis. It is often performed based on physicians’ clinical suspicion. A diagnostic method that can aid in deciding whether this procedure should be performed is necessary. Cytokines are speculated to be associated with neurologic complications. In this study, we aimed to find an indicator of the presence of aseptic meningitis in children with EV71-induced HFMD.

Methods: This cross-sectional study included children with EV71-induced HFMD. The children underwent lumbar puncture due to suspected aseptic meningitis. They were categorized into an aseptic meningitis complicated group (n = 54) and uncomplicated group (n = 47) based on the results of cerebrospinal fluid examination. Healthy children were included as controls (n = 51). The sample serum levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were detected using multiplexed fluorescent bead-based immunoassays.

Results: The levels of all cytokines were significantly higher in children with EV71-induced HFMD complicated with aseptic meningitis than in children with uncomplicated EV71-induced HFMD and controls (p < 0.001). Binary logistic regression analysis demonstrated that IL-6 had the strongest association with aseptic meningitis of all cytokines examined. According to receiver operating characteristic analysis, the optimal cutoff value for IL-6 was 66 pg/mL with maximum sensitivity and specificity.

Conclusions: The results of this study suggest the association between higher production of cytokine and aseptic meningitis among children with EV71-induced HFMD. IL-6 was also suggested as an indicator of aseptic meningitis. Rapid measurement of IL-6 could be useful in deciding whether physicians should perform lumbar puncture on children.

KEYWORDS:

• Enterovirus 71
• hand
• foot and mouth disease
• aseptic meningitis
• cytokines
• interleukin-6
• indicator
• lumbar puncture

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by the Clinical Research Laboratory of The Catholic University of Korea, St. Paul’s Hospital under Grant number PSH-20150301-001.