# Overexpression of IL-8 augments the susceptibility to a hyperinflammatory phenotype in pediatric acute respiratory distress syndrome and correlates with adverse outcomes: a retrospective two-center study conducted in northwest China

**Authors:** Yi Wang, Weikai Wang, Zhe Lv, Haitong Wu, Hua Zhang, Ying Wang, Yong Zhou, Zhangyan Guo, Jingmei Li, Le Ma, Dan Yao, Taining Zhang, Yanqiang Du, Li Liu

PMC · DOI: 10.3389/fped.2026.1626327 · 2026-02-03

## TL;DR

High levels of IL-8 in children with ARDS are linked to worse outcomes and may help predict mortality when combined with other markers.

## Contribution

The study identifies IL-8 overexpression as a prognostic indicator in pediatric ARDS, particularly when combined with other biomarkers.

## Key findings

- IL-8, RAGE, Ang-2, ICAM-1, and SP-D are independent risk factors for mortality in pediatric ARDS.
- IL-8 levels are significantly higher in non-survivors compared to survivors.
- IL-8 is positively correlated with other biomarkers like RAGE, Ang-2, ICAM-1, and SP-D in ARDS children.

## Abstract

The prognosis of acute respiratory distress syndrome (ARDS) varies with inflammatory responses. ARDS patients with a hyperinflammatory phenotype usually have worse alveolar epithelial injury and vascular endothelial injury than those carrying a hypoinflammatory phenotype. Activated neutrophils recruited and migrated in the lung tissue are responsible for stimulating the progression of ARDS. Interleukin-8 (IL-8), as an inflammatory factor, further aggravates lung damage in ARDS.

This was a retrospective study involving 135 ARDS children admitted in two pediatric hospitals in northwest China. They were either classified into mild, moderate and severe groups based on the oxygenation index (OI) or oxygenation saturation index (OSI) within 4-h invasive mechanical ventilation on admission, or the survival and non-survival groups based on the 28-day mortality. Demographic and clinical data were analyzed. Risk factors for the prognosis of PARDS were identified by logistic regression. The correlation of IL-8 level with the identified risk factors was analyzed. Prognostic potential of IL-8 was determined by plotting the receiver operating characteristic (ROC) curves.

IL-8, RAGE, Ang-2, ICAM-1 and SP-D were independent risk factors for the mortality of PARDS. They were significantly higher in the non-survival group than the survival group, showing a potential in predicting mortality in PARDS, especially in the combination (P < 0.05). IL-8 was positively correlated with RAGE, Ang-2, ICAM-1 and SP-D in children with ARDS (P < 0.05).

IL-8 is overexpressed in children with ARDS, showing a prognostic potential particularly in combination with RAGE, Ang-2, ICAM-1 and SP-D in PARDS.

## Linked entities

- **Genes:** CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576], AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177], ANGPT2 (angiopoietin 2) [NCBI Gene 285], ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383], HOXD13 (homeobox D13) [NCBI Gene 3239]
- **Diseases:** acute respiratory distress syndrome (MONDO:0006502), PARDS (MONDO:0100131)

## Full-text entities

- **Genes:** CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, ICAM2 (intercellular adhesion molecule 2) [NCBI Gene 3384] {aka CD102}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, CALCA (calcitonin related polypeptide alpha) [NCBI Gene 796] {aka CALC1, CGRP, CGRP-I, CGRP-alpha, CGRP1, CT}, SFTPD (surfactant protein D) [NCBI Gene 6441] {aka COLEC7, PSP-D, SFTP4, SP-D}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, AGER (advanced glycosylation end-product specific receptor) [NCBI Gene 177] {aka RAGE, SCARJ1, sRAGE}
- **Diseases:** opacities (MESH:D003318), pleural effusion (MESH:D010996), MODS (MESH:D009102), cardiac failure (MESH:D006333), aspiration pneumonia (MESH:D011015), pulmonary inflammatory (MESH:D016726), pneumonia (MESH:D011014), ARDS (MESH:D012128), sepsis (MESH:D018805), neuromuscular blockade (MESH:D020879), OI (MESH:D000860), trauma (MESH:D014947), Inflammatory (MESH:D007249), atelectasis (MESH:D001261), alveolar epithelial injury (MESH:D009375), fluid overload (MESH:D019190), died (MESH:D003643), viral infection (MESH:D014777), infection (MESH:D007239), lung damage (MESH:D008171), COVID-19 (MESH:D000086382), pneumothorax (MESH:D011030), vascular endothelial injury (MESH:D057772), Acute Lung Injury (MESH:D055371), pulmonary edema (MESH:D011654), pancreatitis (MESH:D010195), LIS (MESH:D055370)
- **Chemicals:** H2O (MESH:D014867), nitric oxide (MESH:D009569), oxygen (MESH:D010100)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** ATI — Mus musculus (Mouse), Hybrid cell line (CVCL_U221)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12909583/full.md

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Source: https://tomesphere.com/paper/PMC12909583