摘要： 细胞因子是调节免疫细胞分化、增殖和功能的重要化学介质。白细胞介素-4在多种肝脏疾病的发病与病程进展中起着重要的免疫调节作用,作为一个有着悠久研究历史的细胞因子,近年来其在肝脏疾病的临床与基础研究中有新进展。本文对其在病毒性肝炎、自身免疫性肝病、药物性肝损伤、寄生虫性肝损伤、肝纤维化、肝硬化和原发性肝细胞癌的病程中的影响进行综述。
董旭, 许明晓, 李成忠. 白细胞介素-4在肝脏疾病中的研究进展[J]. 肝脏, 2024, 29(1): 130-133.
| [1] Paul W E. History of interleukin-4[J]. Cytokine, 2015, 75(1):3-7. [2] Gärtner Y, Bitar L, Zipp F, et al. Interleukin-4 as a therapeutic target[J]. Pharmacol Ther, 2023, 242:108348. [3] Qi C, Tan X, Shi Z, et al. Discovery of an oxepine-containing diketopiperazine derivative active against concanavalin a-induced hepatitis[J]. J Nat Prod, 2020, 83(9):2672-2678. [4] Sosa-Jurado F, Sánchez-Reza L, Mendoza-Torres M, et al. Serum Th17 and TNF-α distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals[J]. Eur Cytokine Netw, 2021, 32(2):23-30. [5] Steinmann S, Schoedsack M, Heinrich F, et al. Hepatic ILC2 activity is regulated by liver inflammation-induced cytokines and effector CD4(+) T cells[J]. Sci Rep, 2020, 10(1):1071. [6] Yang W C, Hwang Y S, Chen Y Y, et al. Interleukin-4 supports the suppressive immune responses elicited by regulatory T cells[J]. Front Immunol, 2017, 8:1508. [7] Anthony R M, Kobayashi T, Wermeling F, et al. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway[J]. Nature, 2011, 475(7354):110-113. [8] Palmer L D, Maloney K N, Boyd K L, et al. The innate immune protein S100A9 protects from T-Helper cell type 2-mediated allergic airway inflammation[J]. Am J Respir Cell Mol Biol, 2019, 61(4):459-468. [9] Kassem K M, Ali M, Rhaleb N E. Interleukin 4: its role in hypertension, atherosclerosis, valvular, and nonvalvular cardiovascular diseases[J]. J Cardiovasc Pharmacol Ther, 2020, 25(1):7-14. [10] Townsend E C, Zhang G Y, Ali R, et al. The balance of type 1 and type 2 immune responses in the contexts of hepatitis B infection and hepatitis D infection[J]. J Gastroenterol Hepatol, 2019, 34(4):764-775. [11] 黄俊榕, 吴昌儒, 吴健林. 恩替卡韦联合甘草酸二铵治疗慢性乙型肝炎患者效果研究[J]. 实用肝脏病杂志, 2022, 25(3):327-330. [12] Jiang Y, Ma Z, Xin G, et al. Th1 and Th2 immune response in chronic hepatitis B patients during a long-term treatment with adefovir dipivoxil[J]. Mediators Inflamm, 2010, 2010:143026. [13] Dey D, Pal S, Chakraborty B C, et al. Multifaceted defects in monocytes in different phases of chronic hepatitis B virus infection: lack of restoration after antiviral therapy[J]. Microbiol Spectr, 2022, 10(6):e0193922. [14] 任常军, 武利杰, 思希尧, 等. 新生儿脐血T细胞亚群、γ-干扰素、白细胞介素4与乙型肝炎病毒宫内感染的研究[J]. 中国误诊学杂志, 2018, 13(4):160-164. [15] Li Y, Lian J, Yi L, et al. Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4[J]. Br J Nutr, 2023, 129(10):1812-1819. [16] Dharancy S, Podevin P, Aoudjehane L, et al. Elevated interleukin-4 expression in severe recurrent hepatitis C virus after liver transplantation[J]. Transplantation, 2007, 83(7):906-911. [17] Radmanić L, Bodulić K, Šimičić P, et al. The effect of treatment-induced viral eradication on cytokine and growth factor expression in chronic hepatitis C[J]. Viruses, 2022, 14(8):1613. [18] Ribeiro C R A, De Almeida N A A, Martinelli K G, et al. Cytokine profile during occult hepatitis B virus infection in chronic hepatitis C patients[J/CD]. Virol J, 2021, 18(1):15. [19] Khalil H, Arfa M, El-Masrey S, et al. Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in egypt[J]. J Infect Dev Ctries, 2017, 11(3):261-268. [20] Raus S, Lopez-Scarim J, Luthy J, et al. Hepatic iNKT cells produce type 2 cytokines and restrain antiviral T cells during acute hepacivirus infection[J]. Front Immunol, 2022, 13:953151. [21] Chi G, Feng X X, Ru Y X, et al. TLR2/4 ligand-amplified liver inflammation promotes initiation of autoimmune hepatitis due to sustained IL-6/IL-12/IL-4/IL-25 expression[J]. Mol Immunol, 2018, 99:171-181. [22] Mansour A I, Behairy O G, Abd Almonaem E R, et al. Association of interleukin (IL)-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms with susceptibility to pediatric autoimmune hepatitis type 1[J]. Cytokine, 2018, 110:243-247. [23] Syu B J, Loh C E, Hsueh Y H, et al. Dual roles of IFN-γ and IL-4 in the natural history of murine autoimmune cholangitis: IL-30 and implications for precision medicine[J]. Sci Rep, 2016, 6:34884. [24] 曹逸涵, 孙晓川, 陈志磊, 等. CX3CL1/CCL26-CX3CR1通路在原发性胆汁性胆管炎免疫机制中的作用[J]. 中华临床免疫和变态反应杂志, 2020, 14(3):183-189. [25] Dutta A K, Boggs K, Khimji A K, et al. Signaling through the interleukin-4 and interleukin-13 receptor complexes regulates cholangiocyte TMEM16A expression and biliary secretion[J]. Am J Physiol Gastrointest Liver Physiol, 2020, 318(4):G763-G771. [26] Ryan P M, Bourdi M, Korrapati M C, et al. Endogenous interleukin-4 regulates glutathione synthesis following acetaminophen-induced liver injury in mice[J]. Chem Res Toxicol, 2012, 25(1):83-93. [27] Xu L, Yang Y, Wen Y, et al. Hepatic recruitment of eosinophils and their protective function during acute liver injury[J]. J Hepatol, 2022, 77(2):344-352. [28] Xu L, Yang Y, Jiang J, et al. Eosinophils protect against acetaminophen-induced liver injury through cyclooxygenase-mediated IL-4/IL-13 production[J]. Hepatology, 2023, 77(2):456-465. [29] Mendes E A, Mendes T A, Dos Santos S L, et al. Expression of IL-4, IL-10 and IFN-γ in the liver tissue of cattle that are naturally infected with fasciola hepatica[J]. Vet Parasitol, 2013, 195(1-2):177-182. [30] Seki T, Kumagai T, Kwansa-Bentum B, et al. Interleukin-4 (IL-4) and IL-13 suppress excessive neutrophil infiltration and hepatocyte damage during acute murine schistosomiasis japonica[J]. Infect Immun, 2012, 80(1):159-168. [31] Sharaf O F, Ahmed A A, Ibrahim A F, et al. Modulation of mice immune responses against schistosoma mansoni infection with anti-schistosomiasis drugs: role of interleukin-4 and interferon-gamma[J]. Int J Health Sci (Qassim), 2022, 16(2):3-11. [32] Douglas D B, Beiting D P, Loftus J P, et al. Combinatorial effects of interleukin 10 and interleukin 4 determine the progression of hepatic inflammation following murine enteric parasitic infection[J]. Hepatology, 2010, 51(6):2162-2171. [33] Weng S Y, Wang X, Vijayan S, et al. IL-4 receptor alpha signaling through macrophages differentially regulates liver fibrosis progression and reversal[J]. EBioMedicine, 2018, 29:92-103. [34] 燕奎华, 崔和春, 教波. 慢性乙型肝炎患者肝纤维化指标与IFN-γ、IL4的相关性研究[J]. 肝脏, 2018, 23(8):748-749. [35] Wang Y, Yu W, Shen C, et al. Predictive value of serum IFN-γ inducible protein-10 and IFN-γ/IL-4 ratio for liver fibrosis progression in CHB patients[J/CD]. Sci Rep, 2017, 7:40404. [36] Batsaikhan B, Lu M Y, Yeh M L, et al. Elevated interleukin-4 levels predicted advanced fibrosis in chronic hepatitis C[J]. J Chin Med Assoc, 2019, 82(4):277-281. [37] Wei X, Qian J, Yao W, et al. Hyperactivated peripheral invariant natural killer T cells correlate with the progression of HBV-relative liver cirrhosis[J]. Scand J Immunol, 2019, 90(2):e12775. [38] Del Río C, Ruiz-Pino F, Prados M E, et al. Cannabidiol markedly alleviates skin and liver fibrosis[J]. Front Pharmacol, 2022, 13:981817. [39] Shabbir M, Badshah Y, Khan K, et al. Association of CTLA-4 and IL-4 polymorphisms in viral induced liver cancer[J]. BMC Cancer, 2022, 22(1):518. [40] Kogame M, Nagai H, Shinohara M, et al. Th2 dominance might induce carcinogenesis in patients with HCV-related liver cirrhosis[J]. Anticancer Res, 2016, 36(9):4529-4536. [41] 李彩东, 雷志萍, 张旭强, 等. HBV感染患者外周血标志物与细胞因子高表达的临床意义[J]. 胃肠病学和肝病学杂志, 2020, 29(9):1042-1046. [42] Aboushousha T, Emad M, Rizk G, et al. IL-4, IL-17 and CD163 immunoexpression and IL-6 gene polymorphism in chronic hepatitis C patients and associated hepatocellular carcinoma[J]. Asian Pac J Cancer Prev, 2021, 22(4):1105-1113. [43] Sethi G, Chatterjee S, Rajendran P, et al. Inhibition of STAT3 dimerization and acetylation by garcinol suppresses the growth of human hepatocellular carcinoma in vitro and in vivo[J]. Mol Cancer, 2014, 13:66. [44] Guo C, Ouyang Y, Cai J, et al. High expression of IL-4R enhances proliferation and invasion of hepatocellular carcinoma cells[J]. Int J Biol Markers, 2017, 32(4):e384-e390. |
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