Fifty years since the discovery of interleukin 1: bioogy, pathogenesis and therapy
DOI:
https://doi.org/10.13112/pc.1076Keywords:
INTERLEUKIN-1; INTERLEUKIN 1 RECEPTOR ANTAGONOST PROTEIN; HEREDITARY AUTOINFLAMMATORY DISEASESAbstract
It has been 50 years since the discovery of interleukin 1, a key proinflammatory cytokine for immune reactions in humans, but also an important factor in the pathogenesis of numerous diseases. Among them, in the last 25 years, monogenic autoinflammatory diseases have stood out, as well as other diseases associated with a cytokine storm. The development of drugs that target IL-1 has led to long-term remission and improved prognosis for many rheumatological diseases that in the past had significant complications and, in some cases, even fatal outcomes.
References
1. Auron PE, Webb AC, Rosenwasser LJ, et al. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984;81:7907-11. doi: 10.1073/pnas.81.24.7907
2. Eisenberg SP, Evans RJ, Arend WP, et al. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature. 1990;343:341-6. doi: 10.1038/343341a0
3. Dinarello CA. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat Rev Rheumatol. 2019;15:612-32. doi: 10.1038/s41584-019-0277-8
4. Mantovani A, Dinarello CA, Molgora M, Garlanda C. Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity 2019;50:778-95. doi: 10.1016/j.immuni.2019.03.012
5. Broderick L, Hoffman HM. IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting. Nat Rev Rheumatol. 2022;18:448-63. doi: 10.1038/s41584-022-00797-1
6. Ubhe A. IL-1 receptor antagonist: etiological and drug delivery systems overview. Inflamm Res. 2024;73:2231-47. doi: 10.1007/s00011-024-01960-y
7. Lin B, Goldbach-Mansky R. Pathogenic insights from genetic causes of autoinflammatory inflammasomopathies and interferonopathies. J Allergy Clin Immunol. 2022 Mar;149(3):819-832. doi: 10.1016/j.jaci.2021.10.027
8. Zhang J, Lee PY, Aksentijevich I, Zhou Q. How to Build a Fire: The Genetics of Autoinflammatory Diseases. Annu Rev Genet. 2023 Nov 27;57:245-274. doi: 10.1146/annurev-genet-030123-084224
9. Gagro A. Autoinflamatorne bolesti: od klasifikacije do prognoze. Paediat Croat. 2029;63(Supl 1):236-48.
10. Šestan M, Jelušić M. Kada posumnjati na autoinflamatornu bolest? Reumatizam. 2020;67:36-55. doi: 10.33004/reumatizam-67-1-4
11. Romano M, Arici ZS, Piskin D, et al. The 2021 EULAR/American College of Rheumatology points to consider for diagnosis, management and monitoring of the interleukin-1 mediated autoinflammatory diseases: cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic syndrome, mevalonate kinase deficiency, and deficiency of the interleukin-1 receptor antagonist. Ann Rheum Dis 2022;81:907-921. doi: 10.1136/annrheumdis-2021-221801
12. Ehlers L, Rolfes E, Lieber M, et al. Treat-to-target strategies for the management of familial Mediterranean Fever in children. Pediatr Rheumatol 2023;21:108. doi: 10.1186/s12969-023-00875-y
13. Fautrel B, Mitrovic S, De Matteis A, et al. EULAR/PReS recommendations for the diagnosis and management of Still's disease, comprising systemic juvenile idiopathic arthritis and adult-onset Still's disease. Ann Rheum Dis. 2024;83:1614-27. doi: 10.1136/ard-2024-225851
14. Cetin Gedik K, Arici ZS, Kul Cinar O, Garcia-Bournissen F, Romano M, Demirkaya E. Practical Approach to Diagnosis and Management of IL-1-Mediated Autoinflammatory Diseases (CAPS, TRAPS, MKD, and DIRA). Paediatr Drugs. 2024;26:113-26. doi: 10.1007/s40272-023-00615-5
15. Cron RQ. IL-1 Family Blockade in Cytokine Storm Syndromes. Adv Exp Med Biol. 2024;1448:553-63. doi: 10.1007/978-3-031-59815-9_36
16. Gagro A. Usefulness of interleukin-1 blockade in autoinflammatory diseases. Reumatologia. 2024;62(2):71-73. doi: 10.5114/reum/188546
17. Kilic B, Ozturk A, Karup S, Hacioglu E, Ugurlu S. Efficacy and safety of biologic drugs in Still's disease: a systematic review and network meta-analysis of randomized controlled trials. Rheumatology (Oxford). 2025 Jan 1;64(1):22-31. doi: 10.1093/rheumatology/keae295
18. Malcova H, Strizova Z, Milota T, et al. IL-1 Inhibitors in the Treatment of Monogenic Periodic Fever Syndromes: From the Past to the Future Perspectives. Front Immunol 2021;11:619257. Published 2021 Feb 1. doi:10.3389/fimmu.2020.619257
19. Monteagudo LA, Boothby A, Gertner E. Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome. ACR Open Rheumatol. 2020;2:276-82. doi: 10.1002/acr2.11135
20. Sun H, Van LM, Floch D, et al. Pharmacokinetics and Pharmacodynamics of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis. J Clin Pharmacol. 2016;56:1516-27. doi:10.1002/jcph.754
21. Saper VE, Ombrello MJ, Tremoulet AH, et al. Severe delayed hypersensitivity reactions to IL‐1 and IL‐6 inhibitors link to common HLA‐DRB1*15 alleles. Ann Rheum Dis. 2022;81:406–15. doi: 10.1136/annrheumdis-2021-220578
22. Saper VE, Chen G, Deutsch GH, et al. Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis. 2019;78:1722-31. doi:10.1136/annrheumdis-2019-216040
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Alenka Gagro
This work is licensed under a Creative Commons Attribution 4.0 International License.
By publishing in Paediatria Croatica, authors retain the copyright to their work and grant others the right to use, reproduce, and share their research articles in accordance with the Creative Commons Attribution License (CC BY 4.0), which allows others to distribute and build upon the work as long as they credit the author for the original creation.
