Prognostic and Clinical Significance of Peripheral Blood IL-2, IL-8, and TNF-α in Children with Severe Pneumonia

Severe pediatric pneumonia remains a major clinical burden and early prediction of deterioration is essential for timely risk stratification. This retrospective study evaluated baseline peripheral blood interleukin-2 (IL-2), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and the modified PIRO (mPIRO) score for predicting progression to severe pneumonia in hospitalized children.

We analyzed 143 children with initially non-severe community-acquired pneumonia admitted between October 2020 and February 2022, together with 60 age-matched healthy controls. During hospitalization, 121 children maintained an uncomplicated course and 22 progressed to severe pneumonia. Serum IL-2, IL-8, and TNF-α levels were measured within 24 h of admission using residual serum from routine clinical testing. Logistic regression, ROC analysis, and a nomogram were used to assess predictors and internal cohort discriminative efficacy.

Children with pneumonia had significantly higher IL-2, IL-8, and TNF-α levels than healthy controls (all P < 0.001). Among children with pneumonia, those who progressed to severe disease had higher baseline IL-2 (85.7 ± 14.9 vs 63.0 ± 26.2 pg/mL), TNF-α (91.9 ± 12.5 vs 76.6 ± 9.88 pg/mL), and mPIRO scores (6.0 [5.0-6.0] vs 5.0 [4.0-5.0]; all P < 0.001), whereas IL-8 did not differ significantly (P = 0.622). IL-2, TNF-α, and mPIRO remained independent predictors in multivariable analysis. The combined model showed the highest apparent AUC (0.935, 95% CI 0.877-0.993), compared with mPIRO alone (0.858), TNF-α (0.826), and IL-2 (0.778).

Baseline IL-2, TNF-α, and mPIRO were associated with subsequent progression to severe pneumonia in children. The combined cytokine-mPIRO model may provide preliminary incremental prognostic information, but prospective multicenter validation and comparison with established biomarkers are required before routine clinical implementation.