The diagnostic value of interleukin-36 cytokines in pleural effusions of varying etiologies

Xuxiang Song; Lun Guo; Qipan Zhang; Weili Chen; Wei Fan; Chengna Lv; Pan Tang; Zhaoxing Dong; Xudeng Ye; Qunli Ding

doi:10.1016/j.cca.2023.117533

The diagnostic value of interleukin-36 cytokines in pleural effusions of varying etiologies

Clin Chim Acta. 2023 Sep 1:549:117533. doi: 10.1016/j.cca.2023.117533. Epub 2023 Sep 1.

Authors

Xuxiang Song¹, Lun Guo², Qipan Zhang³, Weili Chen¹, Wei Fan¹, Chengna Lv³, Pan Tang³, Zhaoxing Dong⁴, Xudeng Ye⁵, Qunli Ding⁶

Affiliations

¹ Health Science Center, Ningbo University, Ningbo 315211, China; Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, China.
² Health Science Center, Ningbo University, Ningbo 315211, China.
³ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, China.
⁴ Department of Respiratory and Critical Care Medicine, Ningbo Second Hospital, Ningbo 315010, China.
⁵ Department of Respiratory and Critical Care Medicine, The Cixi Integration of Traditional Chinese and Western Medicine Medical & Health Group, Ningbo 315302, China. Electronic address: 274866227@qq.com.
⁶ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315020, China. Electronic address: dingqunli@nbu.edu.cn.

PMID: 37660939
DOI: 10.1016/j.cca.2023.117533

Abstract

Background: The clinical management of pleural effusion (PE) poses challenges due to its diverse etiologies. The objective of this research was to investigate the concentrations of interleukin-36 (IL-36) cytokines in pleural fluid (PF) from different etiologies and assess their diagnostic efficacy in distinguishing the causes of PE.

Methods: This study enrolled 89 patients with confirmed PE, comprising 11 cases classified as transudate, 24 cases as malignant pleural effusion (MPE), 24 cases as tuberculous pleural effusion (TPE), and 30 cases as parapneumonic pleural effusion (PPE). The PPE group was further subdivided into 20 cases of uncomplicated parapneumonic effusion (UPPE) and 10 cases of complicated parapneumonic effusion (CPPE)/empyema. The concentrations of IL-36 cytokines in the PF of all 89 patients were quantified by the enzyme-linked immunosorbent assay (ELISA).

Results: IL-36α exhibited excellent diagnostic accuracy in TPE, achieving a sensitivity of 91.7 % and specificity of 83.1 %, along with a cut-off value of 435.3 pg/ml. IL-36Ra also demonstrated relatively favorable diagnostic performance in PPE, with a sensitivity of 80.0 % and specificity of 76.3 %, along with a cut-off value of 390.8 pg/ml. Multivariable logistic regression models were successfully developed for both TPE and PPE, confirming their diagnostic utility. Furthermore, the levels of IL-36Ra were notably elevated in CPPE/empyema in comparison to UPPE. Moreover, in PF, IL-36γ exhibited positive associations with both IL-36α and IL-36Ra.

Conclusion: IL-36α and IL-36Ra may serve as novel biomarkers for diagnosing TPE and PPE, respectively. The multivariate models established significantly enhance the diagnostic efficacy of both TPE and PPE. Furthermore, IL-36Ra can function as an indicator for assessing the extent of pleural inflammation. Additionally, the interaction among IL-36 cytokines in PF may contribute to their expression modulation.

Keywords: Biomarker; Diagnosis; Interleukin-36; Pleural effusion.