# The role of IL-18 and IL-33 in the bronchoalveolar lavage fluid of children with severe community-acquired pneumonia complicated with pleural effusion

**Authors:** Yinxia Zhang, Zihao Liu, Yiwei Hong, Li Li, Youzhuo Liang, Liangxin Lin, Wenjian Wang, Heping Wang

PMC · DOI: 10.3389/fped.2025.1560328 · 2025-04-25

## TL;DR

This study examines how certain immune proteins in lung fluid can help predict severe pneumonia complications in children.

## Contribution

The study identifies IL-18, IL-33, and IL-38 as potential biomarkers for predicting pleural effusion in children with severe pneumonia.

## Key findings

- IL-18, IL-33, and the IL-18/IL-38 ratio were significantly elevated in children with pneumonia and pleural effusion.
- These cytokines showed strong predictive power for diagnosing pneumonia complicated with pleural effusion.
- Haemophilus influenzae colonization was linked to reduced levels of IL-18, IL-33, and IL-36α.

## Abstract

To investigate the evaluative role of interleukin (IL)-1 family cytokines in bronchoalveolar lavage fluid (BALF) among children with severe community-acquired pneumonia (SCAP) and identify cytokines with clinical relevance for pediatric SCAP.

Children with SCAP hospitalized at Shenzhen Children's Hospital (2019–2020) were studied. IL-1 family cytokines in the BALF were measured via CBA or ELISA. These cytokines included nine IL-1 family members (IL-1α, IL-1β, IL-1Ra, IL-33, IL-18, IL-37, IL-36α, IL-36Ra, and IL-38) and two receptors (sST2 and IL-18BP). The ratio of proinflammatory cytokines to anti-inflammatory cytokines was analyzed.

In the BALF of children with SCAP complicated with pleural effusion (PE), the levels of IL-18, the IL-18/IL-38 ratio, and the IL-33 level were significantly elevated (P < 0.05). Furthermore, the receiver operating characteristic (ROC) curve indicated that these three markers have strong predictive efficacy for diagnosing SCAP complicated with PE. The levels of members of the IL-1 family, including IL-1α, IL-1β, IL-1Ra, IL-18, and IL-33, and their associated ratios significantly differed across different pathogen groups (P < 0.05). IL-36α and the IL-36α/IL-38 ratio differed significantly between the Haemophilus influenzae (Hi)-positive and -negative groups (P < 0.0001 and 0.0048), with lower levels in the Hi-positive group.

IL-18, IL-33, and IL-38 in BALF may serve as effective markers for predicting the development of PE in pediatric SCAP patients. Additionally, respiratory tract colonization by Hi may diminish the production of specific proinflammatory cytokines, including IL-18, IL-33, and IL-36α, during SCAP.

## Linked entities

- **Proteins:** IL18 (interleukin 18), IL33 (interleukin 33), IL1F10 (interleukin 1 family member 10), IL1A (interleukin 1 alpha), IL1B (interleukin 1 beta), IL1R1 (interleukin 1 receptor type 1), IL37 (interleukin 37), IL36A (interleukin 36 alpha), IL36RN (interleukin 36 receptor antagonist), IL1F10 (interleukin 1 family member 10), CORT (cortistatin), IL18BP (interleukin 18 binding protein)
- **Diseases:** pneumonia (MONDO:0005249)
- **Species:** Haemophilus influenzae (taxon 727)

## Full-text entities

- **Genes:** IL37 (interleukin 37) [NCBI Gene 27178] {aka FIL1, FIL1(ZETA), FIL1Z, IL-1F7, IL-1H, IL-1H4}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, IL36RN (interleukin 36 receptor antagonist) [NCBI Gene 26525] {aka FIL1, FIL1(DELTA), FIL1D, IL-36Ra, IL1F5, IL1HY1}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, IL36A (interleukin 36 alpha) [NCBI Gene 27179] {aka FIL1, FIL1(EPSILON), FIL1E, IL-1F6, IL1(EPSILON), IL1F6}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, IL1F10 (interleukin 1 family member 10) [NCBI Gene 84639] {aka FIL1-theta, FKSG75, IL-1HY2, IL-38, IL1-theta, IL1HY2}, IL1RN (interleukin 1 receptor antagonist) [NCBI Gene 3557] {aka CRMO2, DIRA, ICIL-1RA, IL-1RN, IL-1ra, IL-1ra3}, IL18BP (interleukin 18 binding protein) [NCBI Gene 10068] {aka FVH, IL18BPa}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** SCAP (MESH:D045169), PE (MESH:D010996), inflammatory (MESH:D007249), community-acquired pneumonia (MESH:D003147)
- **Species:** Haemophilus influenzae (species) [taxon 727], Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12063494/full.md

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Source: https://tomesphere.com/paper/PMC12063494