Role of IL-18 in Asthma
Main Article Content
Abstract
Asthma is a common heterogeneous disorder characterized by chronic airway inflammation, remolding and hyperresponsiveness. Although substantial advance has been achieved in understanding its complex pathogenesis, which involves genetic factors, environmental exposures, and immune system imbalances, the effective clinical therapeutics of asthma remains challenging. IL-18, a pleiotropic cytokine of IL-1 superfamily produced mainly by monocyte-macrophage system, is an imperative participant in the pathology of asthma through interacting with IL-18R, and is likely to be the potential targets for the diagnosis and therapeutics of asthma. In this review, we addressed briefly the phenotypes and endotypes of asthma. Then we introduced the regulation mechanisms of the IL-18 production, and summarized the roles of IL-18 in the pathogenesis of different asthma endotypes, in particular emphasizing the roles of IL-18 alone and IL-18 in synergy with other cytokines. Furthermore, we highlighted the effects of IL-18 on airway pathological characteristics and disorder severity of asthma. Finally, we discussed the future research directions and challenges based on IL-18 therapy, which is expected to provide novel ideas for the precise treatment of asthma.
Keywords:
IL-18, asthma, pathogenesis, diagnosis, therapy
Article Details
How to Cite
WANG, Junling et al.
Role of IL-18 in Asthma.
Medical Research Archives, [S.l.], v. 12, n. 12, dec. 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6123>. Date accessed: 06 jan. 2025.
doi: https://doi.org/10.18103/mra.v12i12.6123.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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5. Luo M, Zhao F, Cheng H, Su M, Wang Y. Macrophage polarization: an important role in inflammatory diseases. Front Immunol. 2024;15:1352946. doi:10.3389/fimmu.2024.1352946
6. Wang X, Kong Y, Zheng B, et al. Tissue-resident innate lymphoid cells in asthma. J Physiol. 2023;601(18):3995-4012. doi:10.1113/jp284686
7. Ji T, Li H. T-helper cells and their cytokines in pathogenesis and treatment of asthma. Front Immunol. 2023;14:1149203. doi:10.3389/fimmu.2023.1149203
8. Boonpiyathad T, Sözener ZC, Akdis M, Akdis CA. The role of Treg cell subsets in allergic disease. Asian Pac J Allergy Immunol. 2020;38(3):139-149. doi:10.12932/ap-030220-0754
9. Gutiérrez-Vera C, García-Betancourt R, Palacios PA, et al. Natural killer T cells in allergic asthma: implications for the development of novel immunotherapeutical strategies. Front Immunol. 2024;15:1364774. doi:10.3389/fimmu.2024.1364774
10. Dinarello CA. Interleukin-18. Methods. 1999;19(1):121-32. doi:10.1006/meth.1999.0837
11. Kuruvilla ME, Lee FE, Lee GB. Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease. Clin Rev Allergy Immunol. 2019;56(2):219-233. doi:10.1007/s12016-018-8712-1
12. Hammad H, Lambrecht BN. The basic immunology of asthma. Cell. 2021;184(6):1469-1485. doi:10.1016/j.cell.2021.02.016
13. Wang J, Zhan M, Zhai Y, et al. Allergens induce upregulated IL-18 and IL-18Rα expression in blood Th2 and Th17 cells of patients with allergic asthma. Clin Exp Immunol. 2024;217(1):31-44. doi:10.1093/cei/uxae022
14. Wang Z, Liu Z, Wang L, et al. Altered expression of IL-18 binding protein and IL-18 receptor in basophils and mast cells of asthma patients. Scand J Immunol. 2018;87(5):e12658. doi:10.1111/sji.12658
15. Zhang H, Wang J, Wang L, Xie H, Chen L, He S. Role of IL-18 in atopic asthma is determined by balance of IL-18/IL-18BP/IL-18R. J Cell Mol Med. 2018;22(1):354-373. doi:10.1111/jcmm.13323
16. Ghayur T, Banerjee S, Hugunin M, et al. Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature. 1997;386(6625):619-23. doi:10.1038/386619a0
17. Netea MG, van de Veerdonk FL, Kullberg BJ, Van der Meer JW, Joosten LA. The role of NLRs and TLRs in the activation of the inflammasome. Expert Opin Biol Ther. 2008;8(12):1867-72. doi:10.1517/14712590802494212
18. Triantafilou K, Ward CJK, Czubala M, et al. Differential recognition of HIV-stimulated IL-1β and IL-18 secretion through NLR and NAIP signalling in monocyte-derived macrophages. PLoS Pathog. 2021;17(4):e1009417. doi:10.1371/journal.ppat.1009417
19. Babamale AO, Chen ST. Nod-like Receptors: Critical Intracellular Sensors for Host Protection and Cell Death in Microbial and Parasitic Infections. Int J Mol Sci. 2021;22(21)doi:10.3390/ijms222111398
20. Borges PV, Moret KH, Raghavendra NM, et al. Protective effect of gedunin on TLR-mediated inflammation by modulation of inflammasome activation and cytokine production: Evidence of a multitarget compound. Pharmacol Res. 2017;115:65-77. doi:10.1016/j.phrs.2016.09.015
21. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805-20. doi:10.1016/j.cell.2010.01.022
22. Fukata M, Vamadevan AS, Abreu MT. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Semin Immunol. 2009;21(4):242-53. doi:10.1016/j.smim.2009.06.005
23. Yang J, Zhang M, Luo Y, et al. Protopine ameliorates OVA-induced asthma through modulatingTLR4/ MyD88/NF-κB pathway and NLRP3 inflammasome-mediated pyroptosis. Phytomedicine. 2024;126:155410. doi:10.1016/j.phymed.2024.155410
24. Yang Z, Li X, Wei L, et al. Involucrasin B suppresses airway inflammation in obese asthma by inhibiting the TLR4-NF-κB-NLRP3 pathway. Phytomedicine. 2024;132:155850. doi:10.1016/j.phymed.2024.155850
25. Li M, Wang C, Xu WT, Zhong X. Sodium houttuyfonate plays a protective role in the asthmatic airway by alleviating the NLRP3-related pyroptosis and Th1/Th2 immune imbalance. Mol Immunol. 2023;160:103-111. doi:10.1016/j.molimm.2023.06.013
26. Lu HF, Zhou YC, Hu TY, et al. Unraveling the role of NLRP3 inflammasome in allergic inflammation: implications for novel therapies. Front Immunol. 2024;15:1435892. doi:10.3389/fimmu.2024.1435892
27. Yasuda K, Nakanishi K, Tsutsui H. Interleukin-18 in Health and Disease. Int J Mol Sci. 2019;20(3)doi:10.3390/ijms20030649
28. Sugimoto T, Ishikawa Y, Yoshimoto T, Hayashi N, Fujimoto J, Nakanishi K. Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. J Exp Med. 2004;199(4):535-45. doi:10.1084/jem.20031368
29. Akdis CA, Arkwright PD, Brüggen MC, et al. Type 2 immunity in the skin and lungs. Allergy. 2020;75(7):1582-1605. doi:10.1111/all.14318
30. Chen L, Hou W, Liu F, et al. Blockade of NLRP3/Caspase-1/IL-1β Regulated Th17/Treg Immune Imbalance and Attenuated the Neutrophilic Airway Inflammation in an Ovalbumin-Induced Murine Model of Asthma. J Immunol Res. 2022;2022:9444227. doi:10.1155/2022/9444227
31. Mills KH, Dungan LS, Jones SA, Harris J. The role of inflammasome-derived IL-1 in driving IL-17 responses. J Leukoc Biol. 2013;93(4):489-97. doi:10.1189/jlb.1012543
32. Revu S, Wu J, Henkel M, et al. IL-23 and IL-1β Drive Human Th17 Cell Differentiation and Metabolic Reprogramming in Absence of CD28 Costimulation. Cell Rep. 2018;22(10):2642-2653. doi:10.1016/j.celrep.2018.02.044
33. Ito T, Hirose K, Nakajima H. Bidirectional roles of IL-22 in the pathogenesis of allergic airway inflammation. Allergol Int. 2019;68(1):4-8. doi:10.1016/j.alit.2018.10.002
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