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August 2, 2026Medicine0 citationsOpen Access

Serum inflammatory cytokines IL-1, IL-6, and TNF-α as biomarkers for predicting the severity of pediatric hand-foot-mouth disease: A retrospective cohort study

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XLXiao LiYLYingmei LiZHZhang Hu

Key Result

Elevated serum levels of IL-1, IL-6, and TNF-α were independent risk factors for severe pediatric hand-foot-mouth disease, with IL-1 showing the highest predictive efficacy (AUC 0.87; P=0.001).

Key Points

  • The study investigates the link between inflammatory cytokines and the severity of pediatric hand-foot-mouth disease to identify biomarkers.
  • Retrospective analysis of 240 children with hand-foot-mouth disease, categorized into severe and mild cases.
  • Serum concentrations of IL-1, IL-6, and TNF-α were measured at multiple time points using enzyme-linked immunosorbent assays.
  • Multivariate logistic regression analysis identified significant risk factors associated with disease severity.
  • The severe group exhibited younger ages and prolonged fever duration compared to the mild group (P = .001).
  • Key laboratory indices such as white blood cell count and blood glucose were significantly higher in severe cases (P < .001).
  • Levels of IL-1, IL-6, and TNF-α were significantly elevated in the severe group at all measured time points (P < .05), indicating their efficacy as predictive biomarkers.

Study Design

Type

Cohort (n=240)

Multicenter

No

Structured PICO

Do serum inflammatory cytokines IL-1, IL-6, and TNF-α predict the severity of pediatric hand-foot-mouth disease?

P
Population
240 children with severe (n=120) or mild (n=120) hand-foot-mouth disease admitted to a single center.
O
Outcome
Severity of pediatric hand-foot-mouth disease (severe vs mild)surrogate

Serum IL-1, IL-6, and TNF-α are valuable biomarkers for predicting the severity of pediatric hand-foot-mouth disease, with IL-1 showing the highest predictive efficacy.

Main Result

Effect estimate: AUC 0.87 for IL-1

p-value: p=0.001

Abstract

This study aimed to explore the association between inflammatory cytokines and the severity of pediatric hand-foot-mouth disease (HFMD) and identify predictive biomarkers. We conducted a retrospective analysis of 240 children, including 120 severe HFMD cases and 120 mild HFMD cases admitted to the Linping Campus of The Second Affiliated Hospital of Zhejiang University. Comprehensive clinical data, including demographic information, clinical manifestations, and laboratory parameters, were collected upon hospital admission. Serum concentrations of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α) were quantified using enzyme-linked immunosorbent assays at days 1, 3, and 5 postadmission. Multivariate logistic regression was used to identify significant risk factors. Compared with the mild group, the severe group had a younger age (16.8 ± 10.5 vs 22.2 ± 12.2 months) and longer fever duration and hospital stay (all P = .001). Key laboratory indices (e.g., white blood cell count, blood glucose) were higher in severe cases ( P < .001). IL-1, IL-6, and TNF-α levels in the severe group were significantly elevated at all-time points ( P < .05), with receiver operating characteristic area under the curves of 0.87, 0.81, and 0.72, respectively. Age, fever duration, blood glucose, IL-1, IL-6, and TNF-α were identified as independent risk factors (all P = .001). IL-1, IL-6, and TNF-α are valuable biomarkers for predicting pediatric HFMD severity, with IL-1 showing the highest predictive efficacy, providing a basis for early clinical intervention.

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Cite This Study

Li et al. (2026) conducted a cohort in pediatric hand-foot-mouth disease (HFMD) (n=240). Serum inflammatory cytokines (IL-1, IL-6, and TNF-α) vs. Lower cytokine levels (mild HFMD) was evaluated on Severe hand-foot-mouth disease (AUC 0.87 for IL-1, p=0.001). Elevated serum levels of IL-1, IL-6, and TNF-α were independent risk factors for severe pediatric hand-foot-mouth disease, with IL-1 showing the highest predictive efficacy (AUC 0.87; P=0.001).

synapsesocial.com/papers/6a6eeaaf1b0468a7eeab30a9https://doi.org/10.1097/md.0000000000049982
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