他汀类药物在过敏性疾病中的治疗作用探讨

doi:10.6040/j.issn.1673-3770.0.2022.410

摘要/Abstract

摘要： 过敏性疾病是一类常见的慢性病,其发病率持续升高,严重影响患者生活质量。治疗有效且价格合理的新型药物的研发工作需要持续进行。近年来,他汀类药物被发现除了降低血液中的脂质水平外,还有抗炎、抗氧化、免疫调节等多效作用,一系列的动物实验及临床试验均证实他汀类药物对过敏性炎症有治疗作用。他汀类药物在过敏性疾病中的具体作用机制、临床效果是现在研究的重点,对于该药的临床应用有重要意义。论文将他汀类药物在过敏性疾病的临床干预中的研究进展作一介绍,并综述他汀类药物在过敏性疾病中的作用机制。

关键词: 他汀类药物, 过敏性疾病, 免疫, 血脂异常, 甲羟戊酸

Abstract: Allergic diseases are a common group of chronic conditions with continuously increasing prevalence. These diseases adversely affect the quality of life of patients. The research and development of new drugs with effective treatment and reasonable price need to continue. In recent years, in addition to lowering blood lipid levels, statins have pleiotropic properties and exert anti-inflammatory, antioxidant, and immunomodulatory effects. A series of animal experiments and clinical trials have confirmed the therapeutic effects of statins against allergic inflammation. Their specific mechanism of action and clinical effects in allergic diseases are the focus of current research, which is of great significance for the clinical application of them. In this article, the research progress of clinical intervention of statins in the treatment of allergic diseases is introduced, and the research progress of the therapeutic mechanism of statins in allergic diseases is reviewed.

Key words: Statins, Allergic Diseases, Immunity, Dyslipidemia, Mevalonic acid

中图分类号:

R392.8

董淋,温思露,邓玉琴,陶泽璋. 他汀类药物在过敏性疾病中的治疗作用探讨[J]. 山东大学耳鼻喉眼学报, 2024, 38(1): 106-114.

DONG Lin, WEN Silu, DENG Yuqin, TAO Zezhang. Therapeutic role of statins in allergic diseases[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2024, 38(1): 106-114.

参考文献

[1] Hesse L, Oude Elberink JNG, van Oosterhout AJM, et al. Allergen immunotherapy for allergic airway diseases: use lessons from the past to design a brighter future[J]. Pharmacol Ther, 2022, 237: 108115. doi:10.1016/j.pharmthera.2022.108115
[2] Sánchez-Borges M, Martin BL, Muraro AM, et al. The importance of allergic disease in public health: an iCAALL statement[J]. World Allergy Organ J, 2018, 11(1): 8. doi:10.1186/s40413-018-0187-2
[3] Saadat S, Mohamadian Roshan N, Aslani MR, et al. Rosuvastatin suppresses cytokine production and lung inflammation in asthmatic, hyperlipidemic and asthmatic-hyperlipidemic rat models[J]. Cytokine, 2020, 128: 154993. doi:10.1016/j.cyto.2020.154993
[4] Mohammadian M, Sadeghipour HR, Jahromi GP, et al. Simvastatin and bone marrow-derived mesenchymal stem cells(BMSCs)affects serum IgE and lung cytokines levels in sensitized mice[J]. Cytokine, 2019, 113: 83-88. doi:10.1016/j.cyto.2018.06.016
[5] Wang JY, Yao TC, Tsai YT, et al. Increased dose and duration of statin use is associated with decreased asthma-related emergency department visits and hospitalizations[J]. J Allergy Clin Immunol Pract, 2018, 6(5): 1588-1595.e1. doi:10.1016/j.jaip.2017.12.017
[6] Murphy C, Deplazes E, Cranfield CG, et al. The role of structure and biophysical properties in the pleiotropic effects of statins[J]. Int J Mol Sci, 2020, 21(22): 8745. doi:10.3390/ijms21228745
[7] Dehnavi S, Sohrabi N, Sadeghi M, et al. Statins and autoimmunity: state-of-the-art[J]. Pharmacol Ther, 2020, 214: 107614. doi:10.1016/j.pharmthera.2020.107614
[8] Jiang T, Dai L, Li P, et al. Lipid metabolism and identification of biomarkers in asthma by lipidomic analysis[J]. Biochim Biophys Acta Mol Cell Biol Lipids, 2021, 1866(2): 158853. doi:10.1016/j.bbalip.2020.158853
[9] Ko SH, Jeong J, Baeg MK, et al. Lipid profiles in adolescents with and without asthma: Korea National Health and nutrition examination survey data[J]. Lipids Health Dis, 2018, 17(1): 158. doi:10.1186/s12944-018-0807-4
[10] Sheha, El-Korashi L, AbdAllah AM, et al. Lipid profile and IL-17A in allergic rhinitis: correlation with disease severity and quality of life[J]. J Asthma Allergy, 2021, 14: 109-117. doi:10.2147/JAA.S290813
[11] Kim JH, Lee SW, Yon DK, et al. Association of serum lipid parameters with the SCORAD index and onset of atopic dermatitis in children[J]. Pediatr Allergy Immunol, 2021, 32(2): 322-330. doi:10.1111/pai.13391
[12] Kim JH, Wee JH, Choi HG, et al. Association between statin medication and asthma/asthma exacerbation in a national health screening cohort[J]. J Allergy Clin Immunol Pract, 2021, 9(7): 2783-2791. doi:10.1016/j.jaip.2021.04.014
[13] Tulbah AS. The potential of Atorvastatin for chronic lung diseases therapy[J]. Saudi Pharm J, 2020, 28(11): 1353-1363. doi:10.1016/j.jsps.2020.08.025
[14] Zhang QX, Zhang HF, Lu XT, et al. Statins improve asthma symptoms by suppressing inflammation: a meta-analysis based on RCTs[J]. Eur Rev Med Pharmacol Sci, 2022, 26(22): 8401-8410. doi:10.26355/eurrev_202211_30376
[15] Schoettler N, Strek ME. Recent advances in severe asthma: from phenotypes to personalized medicine[J]. Chest, 2020, 157(3): 516-528. doi:10.1016/j.chest.2019.10.009
[16] Agache I, Beltran J, Akdis C, et al. Efficacy and safety of treatment with biologicals(benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab)for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma[J]. Allergy, 2020, 75(5): 1023-1042. doi:10.1111/all.14221
[17] Hoy SM. Tezepelumab: first approval[J]. Drugs, 2022, 82(4): 461-468. doi:10.1007/s40265-022-01679-2
[18] Maneechotesuwan K, Kasetsinsombat K, Wongkajornsilp A, et al. Role of autophagy in regulating interleukin-10 and the responses to corticosteroids and statins in asthma[J]. Clin Exp Allergy, 2021, 51(12): 1553-1565. doi:10.1111/cea.13825
[19] Hiles SA, Gibson PG, Agusti A, et al. Treatable traits that predict health status and treatment response in airway disease[J]. J Allergy Clin Immunol Pract, 2021, 9(3): 1255-1264.e2. doi:10.1016/j.jaip.2020.09.046
[20] Guerau-de-Arellano M, Britt RD. Sterols in asthma[J]. Trends Immunol, 2022, 43(10): 792-799. doi:10.1016/j.it.2022.08.003
[21] Mehrabi S, Torkan J, Hosseinzadeh M. Effect of atorvastatin on serum periostin and blood eosinophils in asthma - a placebo-controlled randomized clinical trial[J]. J Int Med Res, 2021, 49(12): 3000605211063721. doi:10.1177/03000605211063721
[22] Hellings PW, Steelant B. Epithelial barriers in allergy and asthma[J]. J Allergy Clin Immunol, 2020, 145(6): 1499-1509. doi:10.1016/j.jaci.2020.04.010
[23] Yang L, Fu JR, Zhou YF. Research progress in atopic March[J]. Front Immunol, 2020, 11: 1907. doi:10.3389/fimmu.2020.01907
[24] Scadding GK, Scadding GW. Innate and adaptive immunity: ILC2 and Th2 cells in upper and lower airway allergic diseases[J]. J Allergy Clin Immunol Pract, 2021, 9(5): 1851-1857. doi:10.1016/j.jaip.2021.02.013
[25] Li XL, Li H, Zhang M, et al. Correction to: Exosomes derived from atorvastatin-modified bone marrow dendritic cells ameliorate experimental autoimmune myasthenia gravis by up-regulated levels of IDO/Treg and partly dependent on FasL/Fas pathway[J]. J Neuroinflammation, 2019, 16(1): 119. doi:10.1186/s12974-019-1503-7
[26] Marschall P, Wei RC, Segaud J, et al. Dual function of Langerhans cells in skin TSLP-promoted TFH differentiation in mouse atopic dermatitis[J]. J Allergy Clin Immunol, 2021, 147(5): 1778-1794. doi:10.1016/j.jaci.2020.10.006
[27] Fan PP, Liu Z, Zheng M, et al. Respiratory syncytial virus nonstructural protein 1 breaks immune tolerance in mice by downregulating Tregs through TSLP-OX40/OX40L-mTOR axis[J]. Mol Immunol, 2021, 138: 20-30. doi:10.1016/j.molimm.2021.07.019
[28] Inagaki-Katashiba N, Ito T, Inaba M, et al. Statins can suppress DC-mediated Th2 responses through the repression of OX40-ligand and CCL17 expression[J]. Eur J Immunol, 2019, 49(11): 2051-2062. doi:10.1002/eji.201847992
[29] Kimura H, Francisco D, Conway M, et al. Type 2 inflammation modulates ACE2 and TMPRSS2 in airway epithelial cells[J]. J Allergy Clin Immunol, 2020, 146(1): 80-88.e8. doi:10.1016/j.jaci.2020.05.004
[30] Saikumar Jayalatha AK, Hesse L, Ketelaar ME, et al. The central role of IL-33/IL-1RL1 pathway in asthma: from pathogenesis to intervention[J]. Pharmacol Ther, 2021, 225: 107847. doi:10.1016/j.pharmthera.2021.107847
[31] Nobs SP, Natali S, Pohlmeier L, et al. PPARγ in dendritic cells and T cells drives pathogenic type-2 effector responses in lung inflammation[J]. J Exp Med, 2017, 214(10): 3015-3035. doi:10.1084/jem.20162069
[32] Yagi Y, Kuwahara M, Suzuki J, et al. Glycolysis and subsequent mevalonate biosynthesis play an important role in Th2 cell differentiation[J]. Biochem Biophys Res Commun, 2020, 530(2): 355-361. doi:10.1016/j.bbrc.2020.08.009
[33] Qi XF, Kim DH, Yoon YS, et al. Fluvastatin inhibits expression of the chemokine MDC/CCL22 induced by interferon-gamma in HaCaT cells, a human keratinocyte cell line[J]. Br J Pharmacol, 2009, 157(8): 1441-1450. doi:10.1111/j.1476-5381.2009.00311.x
[34] Liang L, Hur J, Kang JY, et al. Effect of the anti-IL-17 antibody on allergic inflammation in an obesity-related asthma model[J]. Korean J Intern Med, 2018, 33(6): 1210-1223. doi:10.3904/kjim.2017.207
[35] Lee HY, Lee EG, Hur J, et al. Pravastatin alleviates allergic airway inflammation in obesity-related asthma mouse model[J]. Exp Lung Res, 2019, 45(9/10): 275-287. doi:10.1080/01902148.2019.1675807
[36] Wu SQ, Yang RH, Wang GL. Anti-asthmatic effect of pitavastatin through aerosol inhalation is associated with CD4⁺ CD25⁺ Foxp3⁺ T cells in an asthma mouse model[J]. Sci Rep, 2017, 7(1): 6084. doi:10.1038/s41598-017-06476-6
[37] Prado DS, Damasceno LEA, Sonego AB, et al. Pitavastatin ameliorates autoimmune neuroinflammation by regulating the Treg/Th17 cell balance through inhibition of mevalonate metabolism[J]. Int Immunopharmacol, 2021, 91: 107278. doi:10.1016/j.intimp.2020.107278
[38] Blanquiceth Y, Rodríguez-Perea AL, Tabares Guevara JH, et al. Increase of frequency and modulation of phenotype of regulatory T cells by atorvastatin is associated with decreased lung inflammatory cell infiltration in a murine model of acute allergic asthma[J]. Front Immunol, 2016, 7: 620. doi:10.3389/fimmu.2016.00620
[39] Meng LL, Lu Y, Wang XL, et al. Statin therapy protects against abdominal aortic aneurysms by inducing the accumulation of regulatory T cells in ApoE^-/- mice[J]. J Mol Med(Berl), 2022, 100(7): 1057-1070. doi:10.1007/s00109-022-02213-3
[40] Shahbaz SK, Sadeghi M, Koushki K, et al. Regulatory T cells: possible mediators for the anti-inflammatory action of statins[J]. Pharmacol Res, 2019, 149: 104469. doi:10.1016/j.phrs.2019.104469
[41] Rodríguez-Perea AL, Montoya CJ, Olek S, et al. Statins increase the frequency of circulating CD4⁺ FOXP3⁺ regulatory T cells in healthy individuals[J]. J Immunol Res, 2015, 2015: 762506. doi:10.1155/2015/762506
[42] Ha EH, Choi JP, Kwon HS, et al. Endothelial Sox17 promotes allergic airway inflammation[J]. J Allergy Clin Immunol, 2019, 144(2): 561-573.e6. doi:10.1016/j.jaci.2019.02.034
[43] Li HX, Liang XY, Wu JH, et al. Simvastatin attenuates acute lung injury by activation of A2B adenosine receptor[J]. Toxicol Appl Pharmacol, 2021, 422: 115460. doi:10.1016/j.taap.2021.115460
[44] Kavanagh JE, Hearn AP, Dhariwal J, et al. Real-world effectiveness of benralizumab in severe eosinophilic asthma[J]. Chest, 2021, 159(2): 496-506. doi:10.1016/j.chest.2020.08.2083
[45] Fu CH, Tsai WC, Lee TJ, et al. Simvastatin inhibits IL-5-induced chemotaxis and CCR3 expression of HL-60-derived and human primary eosinophils[J]. PLoS One, 2016, 11(6): e0157186. doi:10.1371/journal.pone.0157186
[46] Fu CH, Lee TJ, Huang CC, et al. Simvastatin inhibits the proliferation of HL-60 clone 15- derived eosinophils by inducing the arrest of the cell cycle in the G1/S phase[J]. Eur J Pharmacol, 2019, 856: 172400. doi:10.1016/j.ejphar.2019.05.029
[47] Jha A, Ryu MH, Oo O, et al. Prophylactic benefits of systemically delivered simvastatin treatment in a house dust mite challenged murine model of allergic asthma[J]. Br J Pharmacol, 2018, 175(7): 1004-1016. doi:10.1111/bph.14140
[48] Saadat S, Mokhtari-Zaer A, Hadjzadeh MA, et al. Rosuvastatin affects tracheal responsiveness, bronchoalveolar lavage inflammatory cells, and oxidative stress markers in hyperlipidemic and asthmatic rats[J]. Iran J Allergy Asthma Immunol, 2019, 18(6): 624-638. doi:10.18502/ijaai.v18i6.2175
[49] Saadat S, Boskabady MH. Anti-inflammatory and antioxidant effects of rosuvastatin on asthmatic, hyperlipidemic, and asthmatic-hyperlipidemic rat models[J]. Inflammation, 2021, 44(6): 2279-2290. doi:10.1007/s10753-021-01499-8
[50] Robinson AJ, Kashanin D, O'Dowd F, et al. Fluvastatin and lovastatin inhibit granulocyte macrophage-colony stimulating factor-stimulated human eosinophil adhesion to inter-cellular adhesion molecule-1 under flow conditions[J]. Clin Exp Allergy, 2009, 39(12): 1866-1874. doi:10.1111/j.1365-2222.2009.03334.x
[51] 张雅琪, 刘慧敏, 曹淋曼, 等. MAPK、PI3K-AKT、NF-κB在小鼠过敏性鼻炎中的表达及意义[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 254-259. doi:10.6040/j.issn.1673-3770.0.2021.174 ZHANG Yaqi, LIU Huimin, CAO Linman, et al. Expression and significance of the MAPK, PI3K-AKT, NF-κB pathways of allergic rhinitis in mice[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(3): 254-259. doi:10.6040/j.issn.1673-3770.0.2021.174
[52] Sun Y, Liu YL, Guan XF, et al. Atorvastatin inhibits renal inflammatory response induced by calcium oxalate crystals via inhibiting the activation of TLR4/NF-κB and NLRP3 inflammasome[J]. IUBMB Life, 2020, 72(5): 1065-1074. doi:10.1002/iub.2250
[53] Munoz MA, Jurczyluk J, Simon A, et al. Defective protein prenylation in a spectrum of patients with mevalonate kinase deficiency[J]. Front Immunol, 2019, 10: 1900. doi:10.3389/fimmu.2019.01900
[54] Kim ML, Sung KR, Kwon J, et al. Statins suppress TGF-β2-mediated MMP-2 and MMP-9 expression and activation through RhoA/ROCK inhibition in astrocytes of the human optic nerve head[J]. Invest Ophthalmol Vis Sci, 2020, 61(5): 29. doi:10.1167/iovs.61.5.29
[55] Zhao CC, Xu J, Xie QM, et al. Apolipoprotein E negatively regulates murine allergic airway inflammation via suppressing the activation of NLRP3 inflammasome and oxidative stress[J]. Int Immunopharmacol, 2020, 81: 106301. doi:10.1016/j.intimp.2020.106301
[56] Wang JC, Guo ZQ, Zhang RX, et al. Effects of N-acetylcysteine on oxidative stress and inflammation reactions in a rat model of allergic rhinitis after PM2.5 exposure[J]. Biochem Biophys Res Commun, 2020, 533(3): 275-281. doi:10.1016/j.bbrc.2020.09.022
[57] Han M, Lee DB, Lee SH, et al. Oxidative stress and antioxidant pathway in allergic rhinitis[J]. Antioxidants(Basel), 2021, 10(8): 1266. doi:10.3390/antiox10081266
[58] Zhang CY, Ren XM, Li HB, et al. Simvastatin alleviates inflammation and oxidative stress in rats with cerebral hemorrhage through Nrf2-ARE signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(14): 6321-6329. doi:10.26355/eurrev_201907_18455
[59] Tong HC, Zhang XP, Meng XJ, et al. Simvastatin inhibits activation of NADPH oxidase/p38 MAPK pathway and enhances expression of antioxidant protein in parkinson disease models[J]. Front Mol Neurosci, 2018, 11: 165. doi:10.3389/fnmol.2018.00165
[60] Igde M, Baran P, Oksuz BG, et al. Association between the oxidative status, Vitamin D levels and respiratory function in asthmatic children[J]. Niger J Clin Pract, 2018, 21(1): 63-68. doi:10.4103/njcp.njcp_373_16
[61] Wysocka A, Cybulski M, P Wysokiński A, et al. Paraoxonase 1 activity, polymorphism and atherosclerosis risk factors in patients undergoing coronary artery surgery[J]. J Clin Med, 2019, 8(4): 441. doi:10.3390/jcm8040441
[62] García-Ortiz A, Serrador JM. Nitric oxide signaling in T cell-mediated immunity[J]. Trends Mol Med, 2018, 24(4): 412-427. doi:10.1016/j.molmed.2018.02.002
[63] Holguin F, Grasemann H, Sharma S, et al. L-citrulline as add-on therapy to increase nitric oxide, and to improve asthma control in obese asthmatics[J]. JCI Insight, 2019, 4(24): e131733. doi:10.1172/jci.insight.131733
[64] Yang RQ, Guo PF, Ma Z, et al. Effects of simvastatin on iNOS and caspase3 levels and oxidative stress following smoke inhalation injury[J]. Mol Med Rep, 2020, 22(4): 3405-3417. doi:10.3892/mmr.2020.11413

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed