Mechanisms by which interleukin-18 binding protein regulates the NLRP3 inflammasome in Kawasaki disease-related coronary artery lesions

Wen XU; Shi WANG; Tian-Hua LI

doi:10.7499/j.issn.1008-8830.2605032

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Chinese Journal of Contemporary Pediatrics ›› 2026, Vol. 28 ›› Issue (10) : 1312-1317. DOI: 10.7499/j.issn.1008-8830.2605032

REVIEW

Mechanisms by which interleukin-18 binding protein regulates the NLRP3 inflammasome in Kawasaki disease-related coronary artery lesions

Wen XU ¹ ,
Shi WANG ¹ ,
Tian-Hua LI ²

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Abstract

Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis, with coronary artery lesion (CAL) representing its most serious complication. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a pivotal role in KD-associated CAL. Upon activation, it cleaves and releases mature interleukin-18 (IL-18) and other proinflammatory cytokines, which propagates downstream inflammatory cascades. IL‑18 binding protein (IL‑18BP) is an endogenous high-affinity antagonist. Studies have shown that dysregulation of the IL‑18/IL‑18BP axis, together with aberrant NLRP3 inflammasome activation, contributes to the initiation and progression of coronary artery injury in KD. This review aims to elucidate the positive feedback amplification between IL-18 and the NLRP3 inflammasome in KD-CAL, and the pathways through which IL-18BP regulates the NLRP3 inflammasome by blocking this positive feedback loop, thereby providing a new theoretical basis and potential interventional targets for the treatment of KD.

Key words

Kawasaki disease / Coronary artery lesion / Interleukin-18 binding protein / NOD-like receptor family pyrin domain containing 3 inflammasome / Inflammatory response

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Wen XU , Shi WANG , Tian-Hua LI. Mechanisms by which interleukin-18 binding protein regulates the NLRP3 inflammasome in Kawasaki disease-related coronary artery lesions[J]. Chinese Journal of Contemporary Pediatrics. 2026, 28(10): 1312-1317 https://doi.org/10.7499/j.issn.1008-8830.2605032

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis

[1]	张苗, 杨军, 黄美子. 急性期川崎病患儿血清KNG1、TIMP3水平与冠状动脉病变的关系[J]. 国际检验医学杂志, 2025, 46(17): 2110-2114. DOI: 10.3969/j.issn.1673-4130.2025.17.011 . Cited in this article [1]

[2]	Watts RA, Hatemi G, Burns JC, et al. Global epidemiology of vasculitis[J]. Nat Rev Rheumatol, 2022, 18(1): 22-34. PMCID: PMC8633913. DOI: 10.1038/s41584-021-00718-8 . https://www.ncbi.nlm.nih.gov/pubmed/34853411 Cited in this article [1]

[3]

, Lu

, Wen

, et al. Cathelicidin (LL-37) causes expression of inflammatory factors in coronary artery endothelial cells of Kawasaki disease by activating TLR4-NF-κB-NLRP3 signaling[J]. Immun Inflamm Dis, 2023, 11(9): e1032. PMCID: PMC10521377. DOI: 10.1002/iid3.1032 .

https://www.ncbi.nlm.nih.gov/pubmed/37773705

Cited in this article [1]

[4]	Seki M, Minami T. Kawasaki disease: pathology, risks, and management[J]. Vasc Health Risk Manag, 2022, 18: 407-416. PMCID: PMC9196282. DOI: 10.2147/VHRM.S291762 . https://www.ncbi.nlm.nih.gov/pubmed/35711626 Cited in this article [1]

[5]	Bordea MA, Costache C, Grama A, et al. Cytokine cascade in Kawasaki disease versus Kawasaki-like syndrome[J]. Physiol Res, 2022, 71(1): 17-27. PMCID: PMC8997683. DOI: 10.33549/physiolres.934672 . https://www.ncbi.nlm.nih.gov/pubmed/35043641 Cited in this article [1]

[6]	Lin S, He Y, He L, et al. Randomized trial of adjunctive prednisolone for Kawasaki disease[J]. N Engl J Med, 2026, 394(15): 1480-1490. DOI: 10.1056/NEJMoa2511478 . https://www.ncbi.nlm.nih.gov/pubmed/41985133 Cited in this article [1]

[7]	Afonina IS, Zhong Z, Karin M, et al. Limiting inflammation: the negative regulation of NF-κB and the NLRP3 inflammasome[J]. Nat Immunol, 2017, 18(8): 861-869. DOI: 10.1038/ni.3772 . https://www.ncbi.nlm.nih.gov/pubmed/28722711 Cited in this article [1]

[8]	Baysak E, Yildirim C, Sayar N, et al. The possible role of NLRP3 inflammasome in depression and myocardial infarction comorbidity[J]. J Pers Med, 2023, 13(9): 1295. PMCID: PMC10533058. DOI: 10.3390/jpm13091295 . https://www.ncbi.nlm.nih.gov/pubmed/37763063 Cited in this article [1]

[9]	杨银岳, 赵耀伟, 张君燕, 等. 基于NF-κB/NLRP3炎症通路来探讨脑卒中后抑郁的相关机制[J]. 卒中与神经疾病, 2025, 32(5): 543-548. DOI: 10.3969/j.issn.1007-0478.2025.05.022 . Cited in this article [1]

[10]	Shi J, Gao W, Shao F. Pyroptosis: gasdermin-mediated programmed necrotic cell death[J]. Trends Biochem Sci, 2017, 42(4): 245-254. DOI: 10.1016/j.tibs.2016.10.004 . https://www.ncbi.nlm.nih.gov/pubmed/27932073 Cited in this article [1]

[11]	Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics[J]. Nat Rev Immunol, 2019, 19(8): 477-489. PMCID: PMC7807242. DOI: 10.1038/s41577-019-0165-0 . https://www.ncbi.nlm.nih.gov/pubmed/31036962 Cited in this article [1]

[12]	He Y, Zeng MY, Yang D, et al. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux[J]. Nature, 2016, 530(7590): 354-357. PMCID: PMC4810788. DOI: 10.1038/nature16959 . https://www.ncbi.nlm.nih.gov/pubmed/26814970 Cited in this article [1]

[13]	秦颖, 赵伟. NLRP3炎症小体的负向调控机制[J]. 中国科学（生命科学）, 2018, 48(11): 1187-1196. DOI: 10.1360/N052018-00156 . Cited in this article [1]

[14]	冀青, 郭兴青, 司辉, 等. 儿童川崎病外周血NLRP3炎性小体与细胞因子表达及其临床意义[J]. 青岛大学学报（医学版）, 2025, 61(3): 395-400. DOI: 10.11712/jms.2096-5532.2025.61.074 . Cited in this article [1]

[15]	阮殿瑶. IL‑18和IL‑18BP与STEMI患者急诊PCI术后心肌缺血再灌注损伤的相关性研究[D]. 大理: 大理大学, 2024. Cited in this article [1]

[16]

Huang

, Sun

, Juan

, et al. Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in vitro by inhibiting NLRP3 inflammasome activation[J]. BMC Anesthesiol, 2021, 21(1): 104. PMCID: PMC8022424. DOI: 10.1186/s12871-021-01334-5 .

https://www.ncbi.nlm.nih.gov/pubmed/33823789

Cited in this article [1]

[17]	Tan Y, Ye Y, Huang C, et al. Cigarette smoking induces skeletal muscle atrophy in mice by activated macrophage-mediated pyroptosis[J]. J Inflamm Res, 2025, 18: 2447-2464. PMCID: PMC11847447. DOI: 10.2147/JIR.S497631 . https://www.ncbi.nlm.nih.gov/pubmed/39991657 Cited in this article [1]

[18]	He Y, Hara H, Núñez G. Mechanism and regulation of NLRP3 inflammasome activation[J]. Trends Biochem Sci, 2016, 41(12): 1012-1021. PMCID: PMC5123939. DOI: 10.1016/j.tibs.2016.09.002 . https://www.ncbi.nlm.nih.gov/pubmed/27669650 Cited in this article [1]

[19]

, Ma

, Liu

, et al. The regulatory effect and mechanism of traditional Chinese medicine on the renal inflammatory signal transduction pathways in diabetic kidney disease: a review[J]. Medicine (Baltimore), 2024, 103(38): e39746. PMCID: PMC11419508. DOI: 10.1097/MD.0000000000039746 .

https://www.ncbi.nlm.nih.gov/pubmed/39312356

Cited in this article [1]

[20]	Knorr J, Kaufmann B, Inzaugarat ME, et al. Interleukin-18 signaling promotes activation of hepatic stellate cells in mouse liver fibrosis[J]. Hepatology, 2023, 77(6): 1968-1982. PMCID: PMC9984672. DOI: 10.1002/hep.32776 . https://www.ncbi.nlm.nih.gov/pubmed/36059147 Cited in this article [3]

[21]

Zhang

, Zhang

, Song

, et al. IL‑18BP alleviates anxiety-like behavior induced by traumatic stress via inhibition of the IL‑18R-NLRP3 signaling pathway in a mouse model of hemorrhagic shock and resuscitation[J]. Mol Neurobiol, 2023, 60(1): 382-394. DOI: 10.1007/s12035-022-03085-x .

https://www.ncbi.nlm.nih.gov/pubmed/36269543

Cited in this article [3]

[22]	Shimizu M, Takei S, Mori M, et al. Pathogenic roles and diagnostic utility of interleukin-18 in autoinflammatory diseases[J]. Front Immunol, 2022, 13: 951535. PMCID: PMC9537046. DOI: 10.3389/fimmu.2022.951535 . https://www.ncbi.nlm.nih.gov/pubmed/36211331 Cited in this article [1]

[23]

Mierzchała-Pasierb

, Lipińska-Gediga

, Lewandowski

, et al. Alterations in serum concentration of soluble CD163 within five study days from ICU admission are associated with in-hospital mortality of septic patients: a preliminary study[J]. Int J Environ Res Public Health, 2023, 20(3): 2263. PMCID: PMC9916291. DOI: 10.3390/ijerph20032263 .

https://www.ncbi.nlm.nih.gov/pubmed/36767629

Cited in this article [1]

[24]	Sauer A, Putensen C, Bode C. Immunomodulation by tetracyclines in the critically ill: an emerging treatment option?[J]. Crit Care, 2022, 26(1): 74. PMCID: PMC8951664. DOI: 10.1186/s13054-022-03909-1 . https://www.ncbi.nlm.nih.gov/pubmed/35337355 Cited in this article [1]

[25]

Cattaneo

, Mezzetti

, Lopreiato

, et al. Gene network expression of whole blood leukocytes in dairy cows with different milk yield at dry-off[J]. PLoS One, 2021, 16(12): e0260745. PMCID: PMC8659302. DOI: 10.1371/journal.pone.0260745 .

https://www.ncbi.nlm.nih.gov/pubmed/34882732

Cited in this article [1]

[26]	主云飞, 田璟鸾, 向轩颐, 等. 重症肌无力患者外周血白细胞介素-18和白细胞介素-18结合蛋白的表达及其临床意义[J]. 中国神经免疫学和神经病学杂志, 2025, 32(5): 351-358. DOI: 10.3969/j.issn.1006-2963.2025.05.001 . Cited in this article [1]

[27]

Girard-Guyonvarc'h

, Harel

, Gabay

. The role of interleukin 18/interleukin 18-binding protein in adult-onset still's disease and systemic juvenile idiopathic arthritis[J]. J Clin Med, 2022, 11(2): 430. PMCID: PMC8781628. DOI: 10.3390/jcm11020430 .

https://www.ncbi.nlm.nih.gov/pubmed/35054124

Cited in this article [1]

[28]	李蕙彤, 任鲁宁, 王菲, 等. IL‑18、IL‑18BP、IL‑18R在特应性皮炎患者外周血B淋巴细胞及单核细胞中的表达[J]. 中国医科大学学报, 2024, 53(9): 782-787. DOI: 10.12007/j.issn.0258-4646.2024.09.003 . Cited in this article [1]

[29]	Italiani P, Manca ML, Angelotti F, et al. IL‑1 family cytokines and soluble receptors in systemic lupus erythematosus[J]. Arthritis Res Ther, 2018, 20(1): 27. PMCID: PMC5806463. DOI: 10.1186/s13075-018-1525-z . https://www.ncbi.nlm.nih.gov/pubmed/29422069 Cited in this article [1]

[30]	郭磊, 辛本凯, 唐一鑫, 等. 白细胞介素18结合蛋白在老年炎性和自身免疫性疾病中的研究进展[J]. 国际老年医学杂志, 2022, 43(3): 346-349. DOI: 10.3969/j.issn.1674-7593.2022.03.022 . Cited in this article [2]

[31]

Kyriakoudi

, Rovina

, Koltsida

, et al. Weaning failure in critically ill patients is related to the persistence of sepsis inflammation[J]. Diagnostics (Basel), 2021, 12(1): 92. PMCID: PMC8774440. DOI: 10.3390/diagnostics12010092 .

https://www.ncbi.nlm.nih.gov/pubmed/35054259

Cited in this article [1]

[32]	Sharma BR, Kanneganti TD. NLRP3 inflammasome in cancer and metabolic diseases[J]. Nat Immunol, 2021, 22(5): 550-559. PMCID: PMC8132572. DOI: 10.1038/s41590-021-00886-5 . https://www.ncbi.nlm.nih.gov/pubmed/33707781 Cited in this article [1]

[33]	刘丽萍, 袁勇华, 何学华, 等. 川崎病患儿急性期外周血单个核细胞NLRP3炎症小体的表达及其临床意义[J]. 中国当代儿科杂志, 2019, 21(10): 992-997. PMCID: PMC7389727. DOI: 10.7499/j.issn.1008-8830.2019.10.008 . https://www.ncbi.nlm.nih.gov/pubmed/31642433 Cited in this article [1]

[34]	Alphonse MP, Duong TT, Shumitzu C, et al. Inositol-triphosphate 3-kinase C mediates inflammasome activation and treatment response in Kawasaki disease[J]. J Immunol, 2016, 197(9): 3481-3489. DOI: 10.4049/jimmunol.1600388 . https://www.ncbi.nlm.nih.gov/pubmed/27694492 Cited in this article [1]

[35]	邓斌, 王爱莲, 程波利, 等. NLRP3炎症小体、Cav-1、S1P1在川崎病患儿中的表达及其与冠状动脉损伤的关系[J]. 实用医学杂志, 2025, 41(13): 2094-2099. DOI: 10.3969/j.issn.1006-5725.2025.13.022 . Cited in this article [1]

[36]	马亚鑫, 朱晓伟, 李淑琼, 等. 川崎病冠状动脉病变分子机制的研究进展[J]. 数理医药学杂志, 2025, 38(5): 390-396. DOI: 10.12173/j.issn.1004-4337.202501015 . Cited in this article [1]

[37]	方晶敏. 川崎病患儿血清中IL‑1β、IL‑18的表达水平及临床意义[D]. 南充: 川北医学院, 2022. Cited in this article [1]

[38]	郭永宏, 杨艳峰, 吴新丹, 等. 血清白介素-17A、白介素-18、白介素-9、肾上腺髓质素前体N端20肽和N末端脑钠肽前体水平对急性期川崎病患儿并发冠状动脉病变的预测价值[J]. 中国医学前沿杂志（电子版）, 2020, 12(6): 93-97. DOI: 10.12037/YXQY.2020.06-17 . Cited in this article [1]

[39]	Weng KP, Hsieh KS, Huang SH, et al. Interleukin-18 and coronary artery lesions in patients with Kawasaki disease[J]. J Chin Med Assoc, 2013, 76(8): 438-445. DOI: 10.1016/j.jcma.2013.04.005 . https://www.ncbi.nlm.nih.gov/pubmed/23769880 Cited in this article [1]

[40]

Yang

, Wang

, Ma

, et al. Study on the mechanism of action of HuaZhuoKeLi in modulating LCN2-mediated cellular pyroptosis to ameliorate ulcerative colitis[J]. Sci Rep, 2026, 16(1): 10754. PMCID: PMC13039466. DOI: 10.1038/s41598-026-45841-2 .

https://www.ncbi.nlm.nih.gov/pubmed/41904244

Cited in this article [1]

[41]

Gao

, Fu

, Wang

, et al. Notch4 signaling pathway in a Kawasaki disease mouse model induced by Lactobacillus casei cell wall extract[J]. Exp Ther Med, 2017, 13(6): 3438-3442. PMCID: PMC5450570. DOI: 10.3892/etm.2017.4434 .

https://www.ncbi.nlm.nih.gov/pubmed/28587423

Cited in this article [2]

[42]	Taru V, Szabo G, Mehal W, et al. Inflammasomes in chronic liver disease: hepatic injury, fibrosis progression and systemic inflammation[J]. J Hepatol, 2024, 81(5): 895-910. PMCID: PMC11881887. DOI: 10.1016/j.jhep.2024.06.016 . https://www.ncbi.nlm.nih.gov/pubmed/38908436 Cited in this article [1]

[43]

, Zhou

, Li

, et al. Notch-activated mesenchymal stromal/stem cells enhance the protective effect against acetaminophen-induced acute liver injury by activating AMPK/SIRT1 pathway[J]. Stem Cell Res Ther, 2022, 13(1): 318. PMCID: PMC9288678. DOI: 10.1186/s13287-022-02999-6 .

https://www.ncbi.nlm.nih.gov/pubmed/35842731

Cited in this article [1]

[44]	Huang H, Cui G, Tang H, et al. Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1[J]. Mol Brain, 2019, 12(1): 102. PMCID: PMC6892218. DOI: 10.1186/s13041-019-0523-7 . https://www.ncbi.nlm.nih.gov/pubmed/31796120 Cited in this article [1]

[45]	Jin K, Parreau S, Warrington KJ, et al. Regulatory T cells in autoimmune vasculitis[J]. Front Immunol, 2022, 13: 844300. PMCID: PMC8918523. DOI: 10.3389/fimmu.2022.844300 . https://www.ncbi.nlm.nih.gov/pubmed/35296082 Cited in this article [1]

[46]	李妍, 王雅楠, 霍许花, 等. 外源性IL‑18结合蛋白对大鼠脓毒症相关肺损伤的影响及NLRP3炎症小体在其中的作用[J]. 中华麻醉学杂志, 2024, 44(11): 1391-1396. DOI: 10.3760/cma.j.cn131073.20240708.01121 . Cited in this article [1]

[47]	Geerlinks AV, Dvorak AM, XIAP Deficiency Treatment Consortium. A case of XIAP deficiency successfully managed with tadekinig alfa (rhIL‑18BP)[J]. J Clin Immunol, 2022, 42(4): 901-903. DOI: 10.1007/s10875-022-01236-2 . https://www.ncbi.nlm.nih.gov/pubmed/35304666 Cited in this article [1]

[48]	杜雨, 朱蕾. 成人斯蒂尔病发病机制及治疗药物的研究进展[J/OL]. 医药导报, 2026. (2026-01-12)[2026-04-07]. https://link.cnki.net/urlid/42.1293.R.20260111.1811.014 Cited in this article [1]