Роль интерлейкина-1 в развитии заболеваний человека: перспективы фармакотерапии. Обзор литературы

Насонов Е.Л. Роль интерлейкина-1 в развитии заболеваний человека: перспективы фармакотерапии. Обзор литературы. Терапевтический архив. 2022;94(8):999–1005. DOI: 10.26442/00403660.2022.08.201781

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Nasonov EL. Role of interleukin-1 in human diseases: pharmacotherapy prospects: A review. Terapevticheskii Arkhiv (Ter. Arkh.). 2022;94(8):999–1005. DOI: 10.26442/00403660.2022.08.201781

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Аннотация

По современным представлениям, иммуновоспалительные заболевания человека (ИВЗ) в зависимости от преобладающих механизмов иммунопатогенеза разделяются на 2 основные категории: аутоиммунные и аутовоспалительные. В то же время в патогенезе большинства ИВЗ принимают участие и аутоиммунные, и аутовоспалительные механизмы, сложное взаимодействие которых находит отражение в полиморфизме клинических проявлений, вариантов течения, исходов и эффективности терапии. Предполагается, что при ИВЗ гиперпродукция цитокинов семейства интерлейкина (ИЛ)-1, являющегося одним из ключевых регуляторов врожденного иммунитета, определяет «перекрест» между механизмами аутовоспаления и аутоиммунитета. В настоящее время для подавления патологических эффектов ИЛ-1 в клинической практике используют препараты анакинра – рекомбинантный негликозилированый аналог антагониста рецептора ИЛ-1, блокирующий сигнализацию как ИЛ-1b, так и ИЛ-1a, и канакинумаб – моноклональные антитела к ИЛ-1b. Анализ результатов клинического применения этих препаратов свидетельствует о том, что ингибицию ИЛ-1 следует рассматривать как перспективное направление фармакотерапии системных аутовоспалительных заболеваний и критических состояний, связанных с развитием гипервоспаления, у детей и взрослых.

Ключевые слова: системные аутовоспалительные заболевания, интерлейкин-1, анакинра, канакинумаб, COVID-19

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According to current concepts, human immunoinflammatory diseases (IIDs), depending on the prevailing mechanisms of immunopathogenesis, are divided into two main categories: autoimmune and autoinflammatory. At the same time, both autoimmune and autoinflammatory mechanisms are involved in the pathogenesis of most IIDs, and the complex interaction of these mechanisms is reflected in the polymorphism of clinical presentation, course variants, outcomes and therapy efficacy. It is suggested that in IIDs, overproduction of cytokines of the interleukin (IL)-1 family, which is one of the key regulators of innate immunity, determines the "crossing" between autoinflammation and autoimmunity mechanisms. Currently, anakinra, a recombinant non-glycosylated analog of the IL-1 receptor antagonist that blocks both IL-1b and IL-1a signaling, and canakinumab, a monoclonal antibody to IL-1b, are used in clinical practice to inhibit the pathological effects of IL-1. Analysis of the treatment outcomes with these drugs suggests that IL-1 inhibition should be considered a promising direction of pharmacotherapy of systemic autoinflammatory diseases and critical conditions associated with hyperinflammation in children and adults.

Keywords: systemic autoinflammatory diseases, interleukin-1, anakinra, canakinumab, COVID-19

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Список литературы

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28. Kyriazopoulou E, Huet T, Cavalli G, et al.; International Collaborative Group for Anakinra in COVID-19. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. Lancet Rheumatol. 2021;3(10):e690-7. DOI:10.1016/S2665-9913(21)00216-2
29. Kyriakoulis KG, Kollias A, Poulakou G, et al. The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis. J Clin Med. 2021;10(19):4462. DOI:10.3390/jcm10194462
30. van de Veerdonk FL, Giamarellos-Bourboulis E, Pickkers P, et al. A guide to immunotherapy for COVID-19. Nat Med. 2022;28(1):39-50. DOI:10.1038/s41591-021-01643-9
31. Gilboa M, Bornstein G, Ben-Zvi I, Grossman C. Macrophage activation syndrome complicating rheumatic diseases in adults: case-based review. Rheumatol Int. 2020;40(4):663-9. DOI:10.1007/s00296-019-04393-7
32. Ajeganova S, De Becker A, Schots R. Efficacy of high-dose anakinra in refractory macrophage activation syndrome in adult-onset Still's disease: when dosage matters in overcoming secondary therapy resistance. Ther Adv Musculoskelet Dis. 2020;12:1759720X20974858. DOI:10.1177/1759720X20974858
33. Monteagudo LA, Boothby A, Gertner E. Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome. ACR Open Rheumatol. 2020;2(5):276-82. DOI:10.1002/acr2.11135
34. Caricchio R, Abbate A, Gordeev I, et al. Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021;326(3):230-9. DOI:10.1001/jama.2021.9508
35. Cremer PC, Sheng CC, Sahoo D, et al. Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation. Eur Heart J Open. 2021;1(1):oeab002. DOI:10.1093/ehjopen/oeab002
36. Generali D, Bosio G, Malberti F, et al. Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study. Int J Infect Dis. 2021;104:433-40. DOI:10.1016/j.ijid.2020.12.073
37. Katia F, Myriam DP, Ucciferri C, et al. Efficacy of canakinumab in mild or severe COVID-19 pneumonia. Immun Inflamm Dis. 2021;9(2):399-405. DOI:10.1002/iid3.400
38. Mastroianni A, Greco S, Chidichimo L, et al. Early use of canakinumab to prevent mechanical ventilation in select COVID-19 patients: A retrospective, observational analysis. Int J Immunopathol Pharmacol. 2021;35:20587384211059675. DOI:10.1177/20587384211059675
39. Potalivo A, Montomoli J, Facondini F, et al. Sixty-Day Mortality Among 520 Italian Hospitalized COVID-19 Patients According to the Adopted Ventilatory Strategy in the Context of an Integrated Multidisciplinary Clinical Organization: A Population-Based Cohort Study. Clin Epidemiol. 2020;12:1421-31. DOI:10.2147/CLEP.S278709
40. Ao G, Wang Y, Li A, et al. The effect of canakinumab on clinical outcomes in patients with COVID-19: A meta-analysis. J Infect. 2022;84(6):834-72. DOI:10.1016/j.jinf.2022.03.011

________________________________________________

1. McGonagle D, McDermott MF. A Proposed Classification of the Immunological Diseases. PLoS Med. 2006;3(8):e297. DOI:10.1371/journal.pmed.0030297
2. Szekanecz Z, McInnes IB, Schett G, et al. Autoinflammation and autoimmunity across rheumatic and musculoskeletal diseases. Nat Rev Rheumatol. 2021;17(10):585-95. DOI:10.1038/s41584-021-00652-9
3. Dinarello CA. An expanding role for interleukin-1 blockade fr om gout to cancer. Molecular Med. 2014;20(Suppl. 1):S43-58. DOI:10.2119/molmed.2014.00232
4. Nasonov EL, Eliseev MS. Role of interleukin 1 in the development of human diseases. Rheumatology Science and Practice. 2016;54(1):60-77 (in Russian).
DOI:10.14412/1995-4484-2016-60-77
5. Doria A, Zen M, Bettio S, et al. Autoinflammation and autoimmunity: bridging the divide. Autoimmun Rev. 2012;12(1):22-30. DOI:10.1016/j.autrev.2012.07.018
6. Migliorini P, Italiani P, Pratesi F, et al. The IL-1 family cytokines and receptors in autoimmune diseases. Autoimmun Rev. 2020;19(9):102617. DOI:10.1016/j.autrev.2020.102617
7. Schett G, Dayer JM, Manger B. Interleukin-1 function and role in rheumatic disease. Nat Rev Rheumatol. 2016;12(1):14-24. DOI:10.1038/nrrheum.2016.166
8. Dinarello CA. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat Rev Rheumatol. 2019;15(10):612-32. DOI:10.1038/s41584-019-0277-8
9. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633-52. DOI:10.1038/nrd3800
10. Malcova H, Milota T, Strizova Z, et al. Interleukin-1 Blockade in Polygenic Autoinflammatory Disorders: Wh ere Are We now? Front Pharmacol. 2021;11:619273. DOI:10.3389/fphar.2020.619273
11. Calabrese L, Fiocco Z, Satoh TK, et al. Therapeutic potential of targeting interleukin-1 family cytokines in chronic inflammatory skin diseases. Br J Dermatol. 2022;186(6):925-41. DOI:10.1111/bjd.20975
12. Bettiol A, Lopalco G, Emmi G, et al. Unveiling the Efficacy, Safety, and Tolerability of Anti-Interleukin-1 Treatment in Monogenic and Multifactorial Autoinflammatory Diseases. Int J Mol Sci. 2019;20(8):1898. DOI:10.3390/ijms20081898
13. Cavalli G, Dinarello CA. Anakinra Therapy for Non-cancer Inflammatory Diseases. Front Pharmacol. 2018;9:1157. DOI:10.3389/fphar.2018.01157. Erratum in: Front Pharmacol. 2019;10:148.
14. Stefania S, Colia R, Cinzia R, et al. Off-label use of anti-IL-1 drugs in rheumatic diseases. Int J Immunopathol Pharmacol. 2021;35:20587384211006584. DOI:10.1177/20587384211006584
15. Maniscalco V, Abu-Rumeileh S, Mastrolia MV, et al. The off-label use of anakinra in pediatric systemic autoinflammatory diseases. Ther Adv Musculoskelet Dis. 2020;12:1759720X20959575. DOI:10.1177/1759720X20959575
16. Cvetkovic RS, Keating G. Anakinra. BioDrugs. 2002;16(4):303-11;discussion 313-4. DOI:10.2165/00063030-200216040-00005
17. Gram H. Preclinical characterization and clinical development of ILARIS(®) (canakinumab) for the treatment of autoinflammatory diseases. Curr Opin Chem Biol. 2016;32:1-9. DOI:10.1016/j.cbpa.2015.12.003
18. Gram H. The long and winding road in pharmaceutical development of canakinumab from rare genetic autoinflammatory syndromes to myocardial infarction and cancer. Pharmacol Res. 2020;154:104139. DOI:10.1016/j.phrs.2019.01.023
19. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017;377(12):1119-31. DOI:10.1056/NEJMoa1707914
20. Ridker PM, MacFadyen JG, Everett BM, et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet. 2018;391(10118):319-28. DOI:10.1016/S0140-6736(17)32814-3
21. Nasonov EL, Popkova TV. Atherosclerosis: perspectives of anti-inflammatory therapy. Terapevticheskii Arkhiv (Ter. Arkh.). 2018;90(5):4-12 (in Russian). DOI:10.26442/terarkh20189054-12
22. Soehnlein O, Libby P. Targeting inflammation in atherosclerosis – from experimental insights to the clinic. Nat Rev Drug Discov. 2021;20(8):589-610.
DOI:10.1038/s41573-021-00198-1
23. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-4.
DOI:10.1016/S0140-6736(20)30628-0
24. Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020;383(23):2255-73. DOI:10.1056/NEJMra2026131
25. Vora SM, Lieberman J, Wu H. Inflammasome activation at the crux of severe COVID-19. Nat Rev Immunol. 2021;21(11):694-703. DOI:10.1038/s41577-021-00588-x
26. CORIMUNO-19 Collaborative group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. Lancet Respir Med. 2021;9(3):295-304. DOI:10.1016/S2213-2600(20)30556-7
27. Kyriazopoulou E, Poulakou G, Milionis H, et al. Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nat Med. 2021;27(10):1752-60. DOI:10.1038/s41591-021-01499-z
28. Kyriazopoulou E, Huet T, Cavalli G, et al.; International Collaborative Group for Anakinra in COVID-19. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. Lancet Rheumatol. 2021;3(10):e690-7. DOI:10.1016/S2665-9913(21)00216-2
29. Kyriakoulis KG, Kollias A, Poulakou G, et al. The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis. J Clin Med. 2021;10(19):4462. DOI:10.3390/jcm10194462
30. van de Veerdonk FL, Giamarellos-Bourboulis E, Pickkers P, et al. A guide to immunotherapy for COVID-19. Nat Med. 2022;28(1):39-50. DOI:10.1038/s41591-021-01643-9
31. Gilboa M, Bornstein G, Ben-Zvi I, Grossman C. Macrophage activation syndrome complicating rheumatic diseases in adults: case-based review. Rheumatol Int. 2020;40(4):663-9. DOI:10.1007/s00296-019-04393-7
32. Ajeganova S, De Becker A, Schots R. Efficacy of high-dose anakinra in refractory macrophage activation syndrome in adult-onset Still's disease: when dosage matters in overcoming secondary therapy resistance. Ther Adv Musculoskelet Dis. 2020;12:1759720X20974858. DOI:10.1177/1759720X20974858
33. Monteagudo LA, Boothby A, Gertner E. Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome. ACR Open Rheumatol. 2020;2(5):276-82. DOI:10.1002/acr2.11135
34. Caricchio R, Abbate A, Gordeev I, et al. Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021;326(3):230-9. DOI:10.1001/jama.2021.9508
35. Cremer PC, Sheng CC, Sahoo D, et al. Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation. Eur Heart J Open. 2021;1(1):oeab002. DOI:10.1093/ehjopen/oeab002
36. Generali D, Bosio G, Malberti F, et al. Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study. Int J Infect Dis. 2021;104:433-40. DOI:10.1016/j.ijid.2020.12.073
37. Katia F, Myriam DP, Ucciferri C, et al. Efficacy of canakinumab in mild or severe COVID-19 pneumonia. Immun Inflamm Dis. 2021;9(2):399-405. DOI:10.1002/iid3.400
38. Mastroianni A, Greco S, Chidichimo L, et al. Early use of canakinumab to prevent mechanical ventilation in select COVID-19 patients: A retrospective, observational analysis. Int J Immunopathol Pharmacol. 2021;35:20587384211059675. DOI:10.1177/20587384211059675
39. Potalivo A, Montomoli J, Facondini F, et al. Sixty-Day Mortality Among 520 Italian Hospitalized COVID-19 Patients According to the Adopted Ventilatory Strategy in the Context of an Integrated Multidisciplinary Clinical Organization: A Population-Based Cohort Study. Clin Epidemiol. 2020;12:1421-31. DOI:10.2147/CLEP.S278709
40. Ao G, Wang Y, Li A, et al. The effect of canakinumab on clinical outcomes in patients with COVID-19: A meta-analysis. J Infect. 2022;84(6):834-72. DOI:10.1016/j.jinf.2022.03.011

Авторы

Е.Л. Насонов*1,2

1 ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой», Москва, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*nasonov@irramn.ru

________________________________________________

Evgeny L. Nasonov*1,2

1 Nasonova Research Institute of Rheumatology, Moscow, Russia;
2 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*nasonov@irramn.ru

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