Association Between IL-17 and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

International Journal of Chronic Obstructive Pulmonary Disease Dovepress open access to scientific and medical research International Journal of Chronic Obstructive Pulmonary Disease downloaded from https://www.dovepress.com/ on 27-Aug-2023 For personal use only. Open Access Full Text Article REVIEW Association Between IL-17 and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis Ru Ma 1–3 , Hongling Su 1–3 , Keping Jiao 1–3 , Jian Liu 1,2 1 The First Clinical Medical College of Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of China; 2Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of China; 3Gansu Provincial People’s Hospital, Lanzhou, Gansu Province, People’s Republic of China Correspondence: Jian Liu, Department of Clinical Medicine, the First Clinical Medical College of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou City, Gansu Province, People’s Republic of China, Tel +86 136 0935 4197, Email Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by neutrophils airway infiltration. It is currently known that Interleukin-17 (IL-17) is an important pro-inflammatory factor. It can promote the accumulation of neutrophils and participate in the chronic inflammatory process of COPD. However, the value of IL-17 levels in the diagnosis and assessment of COPD remains controversial. In view of this, we conducted a systematic review and meta-analysis to assess its relevance. Methods: We searched databases such as PubMed, Web of Science, Cochrane Library and Embase to extract original research. Results: A total of 10 studies with 2268 participants were included in this meta-analysis. The results showed that the level of serum IL-17 in patients with stable COPD was significantly higher than that in healthy controls (standard mean difference SMD, 1.59, 95% CI 0.84–2.34; p<0.001). Compared with the stable COPD group, the serum IL-17 level in acute exacerbation (AECOPD) was significantly higher (SMD, 1.78, 95% CI 1.22–2.33; p<0.001). The level of IL-17 in sputum of COPD patients was also higher than that of healthy controls (SMD, 2.03, 95% CI 0.74–3.31; p<0.001). Conclusion: Our results showed that IL-17 levels were elevated in serum and sputum in COPD patients compared with healthy controls, and IL-17 levels increased with disease progression. IL-17 serves as a potential biomarker to indicate the persistence of neutrophilic inflammation and exacerbation of COPD. Keywords: chronic obstructive pulmonary disease, Interleukin-17, proinflammatory factor, meta-analysis Introduction Chronic obstructive pulmonary disease is a common, incurable, heterogeneous disease characterized by persistent airway inflammation and irreversible airflow limitation.1 About 3 million people worldwide die from the disease every year.2 COPD has been reported to be associated with multiple factors, including systemic and local inflammation, air pollution, and a sedentary lifestyle,3–5 Although the pathogenesis of COPD is unknown, it is well known that the chronic inflammatory response of the airways and lung parenchyma caused by cigarette smoke is the main cause of COPD.6,7 The toxic chemicals in cigarette smoke cause abnormal airway inflammation, which triggers the release of chemokines and promotes infiltration of neutrophils and other inflammatory cells into the airways. Accumulated neutrophils can produce and release a variety of pro-inflammatory mediators and enzymes, including neutrophil elastase (NE) and matrix metalloproteinases, which together contribute to the development of chronic bronchitis and emphysema.8–10 Interleukin-17 (IL-17) is considered to be one of the important pro-inflammatory factors involved in the persistent development of COPD airway inflammation. IL-17 is mainly secreted by helper T cells (Th) 17, and induces neutrophil activation by inducing chemokine to produce IL-17.11 Smokers with COPD showed higher levels of IL-17, p53 and plasminogen activator inhibitor-1 (PAI-1) than healthy smokers (HSs) and healthy controls (HCs).12 In experiments using bleomycin-induced inflammation in alveolar basal epithelial cells simulating in vitro inflammation, upregulation of IL-17 International Journal of Chronic Obstructive Pulmonary Disease 2023:18 1681–1690 Received: 20 March 2023 Accepted: 24 July 2023 Published: 2 August 2023 1681 © 2023 Ma et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Dovepress Ma et al promoted alveolar basal epithelial cell motility and increased production of p53 and PAI-1. By raising p53 and PAI-1, IL17 encourages neutrophil infiltration and lung damage. Alveolar epithelial cells can undergo apoptosis when exposed to both p53 and PAI-1; however, PAI-1 prevents neutrophil apoptosis and fibrinolysis in lung tissue. Additionally, IL-17 stimulates the production of IL-8, granulocyte-colony stimulating factor (G-CSF), and C–X–C motif chemokine ligand 2 (CXCL2), which draws in neutrophils and causes them to produce neutrophil elastase and myeloperoxidase, leading to the breakdown of the alveolar wall and the development of emphysema. Meanwhile, IL-17 was also found to promote airway remodeling in COPD. COPD-related lung structural remodeling can result in permanent airflow obstruction.13 In addition, cigarette smoke stimulation leads to increased IL-17 secretion in COPD patients, making COPD acutely exacerbated and thus contributing to disease progression.14 IL-17 promotes inflammatory response and participates in the pathological process of autoimmune diseases.15–17 Overproduction of IL-17 induces the expression of a large number of inflammatory factors, which may lead to conditions such as reduced tissue flexibility and tissue fibrosis.18 In rheumatoid arthritis (RA), IL-17 acts locally on synovial cells and osteoblasts, causing synovitis and joint destruction.19 In studies related to periodontitis it has been reported that neutrophil infiltration, triggering upregulation of IL17/Th17 responses, and Th17-driven mucosal inflammation lead to destruction of tooth-supporting bone.20 It has also been reported that the pro-inflammatory cascade controlled by the IL23/IL-17 axis is thought to be the most important factor in the immunopathogenesis of psoriasis. il-23 plays a role in the differentiation and activation of Th 17 cells. 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