lvrachЛечащий ВрачLechaschi Vrach1560-51752687-1181ООО «Издательство "Открытые системы"»10.51793/OS.2023.26.5.007lvrach-1073Research ArticleАКТУАЛЬНАЯ ТЕМАTOPICAL THEMEДва полюса антивоспалительного действия азитромицинаTwo poles of the anti-inflammatory action of azithromycinhttps://orcid.org/0000-0002-6081-1740ЛазареваЕ. Н.LazarevaE. N.

Лазарева Елена Николаевна, д.м.н., ведущий научный сотрудник клинического отдела 

111123, Москва, ул. Новогиреевская, 3а

Elena N. Lazareva, Dr. of Sci. (Med.), Leading Researcher of the Clinical Department 

3a Novogireevskaya str., Moscow, 111123

elniklazareva@yandex.ruhttps://orcid.org/0000-0002-6539-4878ПонежеваЖ. Б.PonezhevaZh. B.

Понежева Жанна Бетовна, д.м.н., заведующая клиническим отделом инфекционной патологии 

111123, Москва, ул. Новогиреевская, 3а

Zhanna B. Ponezheva, Dr. of Sci. (Med.), Head of the Clinical Department of Infectious Pathology

3a Novogireevskaya str., Moscow, 111123

doktorim@mail.ruhttps://orcid.org/0009-0007-5629-3972КузнецоваЮ. В.KuznetsovaYu. V.

Кузнецова Юлия Васильевна, ординатор клинического отдела 

111123, Москва, ул. Новогиреевская, 3а

Yuliya V. Kuznetsova, clinical resident of the Clinical Department 

3a Novogireevskaya str., Moscow, 111123

Juliavpavluk@mail.ruФедеральное бюджетное учреждение науки Центральный научно-исследовательский институт эпидемиологии РоспотребнадзораРоссияFederal Budgetary Institution of Science Central Research Institute of Epidemiology of Rospotrebnadzor, Russian Inspectorate for the Protection of Consumer Rights and Human Well-BeingRussian Federation202318072023054247Copyright © Лазарева Е.Н., Понежева Ж.Б., Кузнецова Ю.В., 20232023Лазарева Е.Н., Понежева Ж.Б., Кузнецова Ю.В.Lazareva E.N., Ponezheva Z.B., Kuznetsova Y.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.lvrach.ru/jour/article/view/1073

Прорыв в лечении инфекционных заболеваний произошел с началом эры антибиотиков. Эпидемиологические исследования в отношении внутриклеточных возбудителей, таких как микоплазмы, хламидии, кампилобактрии и легионеллы, в XX веке послужили стимулом для разработки и внедрения в клинику новых антибиотиков из группы макролидов, обладающих улучшенными фармакокинетическими и микробиологическими параметрами. Высокая биодоступность, низкие дозировки и малая кратность введения, широкий спектр действия на патогены, хорошая клиническая и биологическая переносимость новых генераций макролидов способствовали улучшению клинической эффективности при лечении многих инфекционных болезней и бактериальных осложнений в хирургической практике. На сегодняшний день существуют три поколения представителей этой группы, одним из них является азитромицин. Данный антибиотик получен в результате модификации эритромицина путем включения атома азота в лактонное кольцо между 9-м и 10-м атомами углерода, при этом кольцо превращается в 15-членное. Способность азитромицина концентрироваться в макрофагах, влиять на белки барьерной активности эпителия дыхательных путей, проявлять антифибротический эффект с ремоделированием соединительной ткани, а также проявлять противовирусную активность, антиоксидантное и иммуномодулирующее действие позволяет позиционировать этот макролид как перспективное противовоспалительное фармакологическое средство с широким спектром применения при различных патологических состояниях. В последнее десятилетие прогрессивные клинические исследования и исследования in vitro свидетельствуют о растущем признании фармакологического профиля азитромицина как лекарственного препарата.

A breakthrough in the treatment of infectious diseases occurred with the advent of the era of antibiotics. Epidemiological studies on intracellular pathogens such as mycoplasmas, chlamydia, campylobacter and legionella in the 20th century served as an incentive for the development and introduction into the clinic of new macrolide antibiotics with improved pharmacokinetic and microbiological parameters. High bioavailability, low dosages and low frequency of administration, a wide spectrum of action on pathogens, good clinical and biological tolerance of new generations of macrolides contributed to the improvement of clinical efficacy in the treatment of many infectious diseases and bacterial complications in surgical practice. To date, there are three generations of representatives of this group, one of them is azithromycin. This antibiotic was obtained by modifying erythromycin by including a nitrogen atom in the lactone ring between the 9th and 10th carbon atoms, while the ring becomes 15-membered. The ability of azithromycin to concentrate in macrophages, affect proteins of the barrier activity of the respiratory tract epithelium, exhibit an antifibrotic effect with the ability to remodel connective tissue, as well as exhibit antiviral activity, antioxidant and immunomodulatory effects, allows positioning this macrolide as a promising anti-inflammatory pharmacological agent with a wide range of applications in various pathological conditions states. In the last decade, progressive clinical and in vitro studies have indicated a growing acceptance of the pharmacological profile of azithromycin as a drug.

азитромицинзонулинфибробластыметаллопротеазыолигодендроцитыazithromycinzonulinfibroblastsmetalloproteasesoligodendrocytesReferencesPeters D. H., Friedel H. A., Mctavish D. Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy // Drugs. 1992; 44: 750-799. https://doi.org/10.2165/00003495-19924405000007.Peters D. H., Friedel H. A., Mctavish D. Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy // Drugs. 1992; 44: 750-799. https://doi.org/10.2165/00003495-19924405000007.Kong F. Y., Rupasinghe T. W., Simpson J. A., et al. Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men // PloS One. 2017; 12 (3): e0174372. https://doi.org/10.1371/journal.pone.0174372.e0174372.Kong F. Y., Rupasinghe T. W., Simpson J. A., et al. Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men // PloS One. 2017; 12 (3): e0174372. https://doi.org/10.1371/journal.pone.0174372.e0174372.Heidary M., Samangani A. E., Kargari A., et al. Mechanism of action, resistance, synergism, and clinical implications of azithromycin // J Clin Lab Anal. 2022; 36 (6): e24427. https://doi.org/10.1002/jcla.24427.Heidary M., Samangani A. E., Kargari A., et al. Mechanism of action, resistance, synergism, and clinical implications of azithromycin // J Clin Lab Anal. 2022; 36 (6): e24427. https://doi.org/10.1002/jcla.24427.Aghapour M., Raee P., Moghaddam S. J., et al. Airway epithelial barrier dysfunction in chronic obstructive pulmonary disease: role of cigarette smoke exposure // Am J Respir Cell Mol Biol. 2018; 58 (2): 157-169. https://doi.org/10.1165/rcmb.2017-0200TR.Aghapour M., Raee P., Moghaddam S. J., et al. Airway epithelial barrier dysfunction in chronic obstructive pulmonary disease: role of cigarette smoke exposure // Am J Respir Cell Mol Biol. 2018; 58 (2): 157-169. https://doi.org/10.1165/rcmb.2017-0200TR.Song Y., Fu W., Zhang Y., et al. Azithromycin ameliorated cigarette smokeinduced airway epithelial barrier dysfunction by activating Nrf2/GCL/ GSH signaling pathway // Respir Res. 2023; 24: 69. https://doi.org/10.1186/s12931-023-02375-9.Song Y., Fu W., Zhang Y., et al. Azithromycin ameliorated cigarette smokeinduced airway epithelial barrier dysfunction by activating Nrf2/GCL/ GSH signaling pathway // Respir Res. 2023; 24: 69. https://doi.org/10.1186/s12931-023-02375-9.Firth A., Prathapan P. Azithromycin: the first broad-spectrum therapeutic // Eur J Med Chem. 2020; 207: 112739. https://doi.org/10.1016/j.ejmech.2020.112739.Firth A., Prathapan P. Azithromycin: the first broad-spectrum therapeutic // Eur J Med Chem. 2020; 207: 112739. https://doi.org/10.1016/j.ejmech.2020.112739.Montón C., Prina E., Pomares X., et al. Nebulized colistin and continuous cyclic azithromycin in severe COPD patients with chronic bronchial infection due to pseudomonas aeruginosa: a retrospective cohort study // Int J Chron Obstruct Pulmon Dis. 2019; 14: 2365-2373. https://doi.org/10.2147/COPD.S209513.Montón C., Prina E., Pomares X., et al. Nebulized colistin and continuous cyclic azithromycin in severe COPD patients with chronic bronchial infection due to pseudomonas aeruginosa: a retrospective cohort study // Int J Chron Obstruct Pulmon Dis. 2019; 14: 2365-2373. https://doi.org/10.2147/COPD.S209513.Albert R. K., Connett J., Bailey W. C., et al. Azithromycin for prevention of exacerbations of COPD // N Engl J Med. 2011; 365 (8): 689-698. https://doi.org/10.1056/NEJMoa1104623.Albert R. K., Connett J., Bailey W. C., et al. Azithromycin for prevention of exacerbations of COPD // N Engl J Med. 2011; 365 (8): 689-698. https://doi.org/10.1056/NEJMoa1104623.Persson H. L., Vainikka L. K., Sege M., et al. Leaky lysosomes in lung transplant macrophages: azithromycin prevents oxidative damage // Respir Res. 2012; 13 (1): 83. https://doi.org/10.1186/1465-9921-13-83.Persson H. L., Vainikka L. K., Sege M., et al. Leaky lysosomes in lung transplant macrophages: azithromycin prevents oxidative damage // Respir Res. 2012; 13 (1): 83. https://doi.org/10.1186/1465-9921-13-83.Joelsson J. P., Kricker J. A., Arason A.J., et al. Azithromycin ameliorates sulfur dioxide-induced airway epithelial damage and inflammatory responses // Respir Res. 2020; 21 (1): 233. https://doi.org/10.1186/s12931020-01489-8.Joelsson J. P., Kricker J. A., Arason A.J., et al. Azithromycin ameliorates sulfur dioxide-induced airway epithelial damage and inflammatory responses // Respir Res. 2020; 21 (1): 233. https://doi.org/10.1186/s12931020-01489-8.Arason A. J., Joelsson J. P., Valdimarsdottir B., et al. Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia // Respir Res. 2019; 20 (1): 129. https://doi.org/10.1186/s12931019-1101-3.Arason A. J., Joelsson J. P., Valdimarsdottir B., et al. Azithromycin induces epidermal differentiation and multivesicular bodies in airway epithelia // Respir Res. 2019; 20 (1): 129. https://doi.org/10.1186/s12931019-1101-3.Jain S., Durugkar S., Saha P., et al. Effects of intranasal azithromycin on features of cigarette smoke-induced lung inflammation // Eur J Pharmacol. 2022; 915: 174467. https://doi.org/10.1016/j.ejphar.2021.174467.Jain S., Durugkar S., Saha P., et al. Effects of intranasal azithromycin on features of cigarette smoke-induced lung inflammation // Eur J Pharmacol. 2022; 915: 174467. https://doi.org/10.1016/j.ejphar.2021.174467.Naderi N., Farias R., Abou Rjeili M., et al. Investigating the effect of pretreatment with azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke // Exp Lung Res. 2021; 47 (2): 98-109. https://doi.org/10.1080/01902148.2020.1857470.Naderi N., Farias R., Abou Rjeili M., et al. Investigating the effect of pretreatment with azithromycin on inflammatory mediators in bronchial epithelial cells exposed to cigarette smoke // Exp Lung Res. 2021; 47 (2): 98-109. https://doi.org/10.1080/01902148.2020.1857470.Dalle-Donne I., Garavaglia M. L., Colombo G., et al. Cigarette smoke and glutathione: focus on in vitro cell models // Toxicol In Vitro. 2020; 65: 104818. https://doi.org/10.1016/j.tiv.2020.104818.Dalle-Donne I., Garavaglia M. L., Colombo G., et al. Cigarette smoke and glutathione: focus on in vitro cell models // Toxicol In Vitro. 2020; 65: 104818. https://doi.org/10.1016/j.tiv.2020.104818.Hassanein E. H. M., Sayed G.A., Alzoghaibi A. M., et al. Azithromycin mitigates cisplatin-induced lung oxidative stress, inflammation and necroptosis by upregulating SIRT1, PPARγ, and Nrf2/HO-1 signaling // Pharmaceuticals-Base. 2022; 16 (1): 52. https://doi.org/10.3390/ph16010052.Hassanein E. H. M., Sayed G.A., Alzoghaibi A. M., et al. Azithromycin mitigates cisplatin-induced lung oxidative stress, inflammation and necroptosis by upregulating SIRT1, PPARγ, and Nrf2/HO-1 signaling // Pharmaceuticals-Base. 2022; 16 (1): 52. https://doi.org/10.3390/ph16010052.Nagano T., Yamaguchi T., Kajiyama S., et al. Effect of Azithromycin on Proinflammatory Cytokine Production in Gingival Fibroblasts and the Remodeling of Periodontal Tissue // J Clin Med. 2021; 10 (1): 99. https://doi.org/10.3390/jcm10010099.Nagano T., Yamaguchi T., Kajiyama S., et al. Effect of Azithromycin on Proinflammatory Cytokine Production in Gingival Fibroblasts and the Remodeling of Periodontal Tissue // J Clin Med. 2021; 10 (1): 99. https://doi.org/10.3390/jcm10010099.Zhang, Y., Ge, L., Song, G., et al. Azithromycin alleviates the severity of rheumatoidarthritis by targeting the unfolded protein responsecomponent of glucose-regulated protein 78 (GRP78) // Br J Pharmacol. 2022; 179 (6): 1201-1219. https://doi.org/10.1111/bph.15714.Zhang, Y., Ge, L., Song, G., et al. Azithromycin alleviates the severity of rheumatoidarthritis by targeting the unfolded protein responsecomponent of glucose-regulated protein 78 (GRP78) // Br J Pharmacol. 2022; 179 (6): 1201-1219. https://doi.org/10.1111/bph.15714.Ramarao S., PangY., Carter K., Bhatt A. Azithromycin Protects Oligodendrocyte Progenitor Cells against Lipopolysaccharide-Activated Microglia-Induced Damage // Dev Neurosci. 2022; 44 (1): 1-12. https://doi.org/10.1159/000519874/.Ramarao S., PangY., Carter K., Bhatt A. Azithromycin Protects Oligodendrocyte Progenitor Cells against Lipopolysaccharide-Activated Microglia-Induced Damage // Dev Neurosci. 2022; 44 (1): 1-12. https://doi.org/10.1159/000519874/.Menzel M., Akbarshahi H., Bjermer L., Uller L. Azithromycin induces antiviral effects in cultured bronchial epithelial cells from COPD patients // Sci Rep. 2016; 28 (6): 28698. https://doi.org/10.1038/srep28698.Menzel M., Akbarshahi H., Bjermer L., Uller L. Azithromycin induces antiviral effects in cultured bronchial epithelial cells from COPD patients // Sci Rep. 2016; 28 (6): 28698. https://doi.org/10.1038/srep28698.Bosseboeuf E., Aubry M., Nhan T., et al. Azithromycin inhibits the replication of Zika virus // J Antivir Antiretrovir. 2018; 10 (1): 6-11. https://doi.org/10.4172/1948-5964.1000173.Bosseboeuf E., Aubry M., Nhan T., et al. Azithromycin inhibits the replication of Zika virus // J Antivir Antiretrovir. 2018; 10 (1): 6-11. https://doi.org/10.4172/1948-5964.1000173.Retallack H., Di Lullo E., Arias C., et al. Zika virus cell tropism in the developing human brain and inhibition by azithromycin // Proc Natl Acad Sci USA. 2016; 113 (50): 14408-14413. https://doi.org/10.1073/pnas.1618029113.Retallack H., Di Lullo E., Arias C., et al. Zika virus cell tropism in the developing human brain and inhibition by azithromycin // Proc Natl Acad Sci USA. 2016; 113 (50): 14408-14413. https://doi.org/10.1073/pnas.1618029113.Kouznetsova J., Sun W., Martínez-Romero C., et al. Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs // Emerg Microb Infect. 2014; 3 (12): e84. https://doi.org/10.1038/emi.2014.88.Kouznetsova J., Sun W., Martínez-Romero C., et al. Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs // Emerg Microb Infect. 2014; 3 (12): e84. https://doi.org/10.1038/emi.2014.88.Du X., Zuo X., Meng F., et al. Combinatorial screening of a panel of FDA-approved drugs identifies several candidates with anti-Ebola activities // Biochem Biophys Res Commun. 2020; 522 (4): 862-868. https://doi.org/10.1016/j.bbrc.2019.11.065.Du X., Zuo X., Meng F., et al. Combinatorial screening of a panel of FDA-approved drugs identifies several candidates with anti-Ebola activities // Biochem Biophys Res Commun. 2020; 522 (4): 862-868. https://doi.org/10.1016/j.bbrc.2019.11.065.Li C., Zu S., Deng Y.Q., et al. Azithromycin protects against Zika virus infection by upregulating virus-induced type I and III interferon responses // Antimicrob Agents Chemother. 2019; 63 (12): e00394-19. https://doi.org/10.1128/aac.00394-19.Li C., Zu S., Deng Y.Q., et al. Azithromycin protects against Zika virus infection by upregulating virus-induced type I and III interferon responses // Antimicrob Agents Chemother. 2019; 63 (12): e00394-19. https://doi.org/10.1128/aac.00394-19.Tran D. H., Sugamata R., Hirose T., et al. Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process. J. Antibiot (Tokyo). 2019; 72 (10): 759-768. https://doi.org/10.1038/s41429-019-0204-x.Tran D. H., Sugamata R., Hirose T., et al. Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process. J. Antibiot (Tokyo). 2019; 72 (10): 759-768. https://doi.org/10.1038/s41429-019-0204-x.Touret F., Gilles M., Barral K., et al. In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication // Sci Rep. 2020; 10 (1): 13093. https://doi.org/10.1038/s41598020-70143-6.Touret F., Gilles M., Barral K., et al. In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication // Sci Rep. 2020; 10 (1): 13093. https://doi.org/10.1038/s41598020-70143-6.Damle B., Vourvahis M., Wang E., et al. Clinical pharmacology perspectives on the antiviral activity of azithromycin and use in COVID-19 // Clin Pharmacol. Ther. 2020; 108 (2): 201-211. https://doi.org/10.1002/cpt.1857.Damle B., Vourvahis M., Wang E., et al. Clinical pharmacology perspectives on the antiviral activity of azithromycin and use in COVID-19 // Clin Pharmacol. Ther. 2020; 108 (2): 201-211. https://doi.org/10.1002/cpt.1857.Wilson D.W., Goodman C. D., Sleebs B. E., et al. Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum // BMC Biol. 2015; 18 (13): 52. https://doi.org/10.1186/s12915015-0162-0.Wilson D.W., Goodman C. D., Sleebs B. E., et al. Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum // BMC Biol. 2015; 18 (13): 52. https://doi.org/10.1186/s12915015-0162-0.Khezri M. R., Zolbanin N. M., Ghasemnejadberenji N. M., Jafari R. Azithromycin: Immunomodulatory and antiviral properties for SARS-CoV-2 infection // Eur J Pharmacol. 2021; 15; 905: 174191. https://doi.org/10.1016/j.ejphar.2021.174191.Khezri M. R., Zolbanin N. M., Ghasemnejadberenji N. M., Jafari R. Azithromycin: Immunomodulatory and antiviral properties for SARS-CoV-2 infection // Eur J Pharmacol. 2021; 15; 905: 174191. https://doi.org/10.1016/j.ejphar.2021.174191.

The authors declare that there are no conflicts of interest present.