<?xml version="1.1" encoding="utf-8"?>
<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">JCNR</journal-id><journal-title-group><journal-title>Journal of Clinical and Nursing Research</journal-title></journal-title-group><issn>2208-3685</issn><eissn>2208-3693</eissn><publisher><publisher-name>Bio-Byword Scientific Publishing Pty. Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.26689/jcnr.v9i9.12338</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Reclassification of Cytokine-Based Immune- Mediated Inflammatory Diseases: Mechanisms and Therapeutic Advances of IL-1-Driven Inflammatory Diseases</title><url>https://artdesignp.com/journal/JCNR/9/9/10.26689/jcnr.v9i9.12338</url><author>DaiXin,LiDan,LiYi,CaoBoran,HuangDongzhe,YuanQi,LiBin</author><pub-date pub-type="publication-year"><year>2025</year></pub-date><volume>9</volume><issue>9</issue><history><date date-type="pub"><published-time>2025-10-17</published-time></date></history><abstract>Immune-mediated inflammatory diseases (IMIDs) represent a heterogeneous group of disorders driven by immune dysregulation, involving multiple organ systems and characterized by substantial clinical diversity. Traditional classification based on affected organs fails to capture shared pathogenic mechanisms and impedes the development of unified therapeutic strategies. In recent years, reclassification of IMIDs according to the dominance of key cytokine hubs has emerged as a focus of research. Interleukin-1 (IL-1), crucial in triggering and maintaining innate immune reactions, is key to the onset and continuation of inflammation. Aberrant activation of the IL-1 axis serves as a pathogenic driver in several prototypical auto-inflammatory diseases (AIDs) and plays a role in the development of inflammatory diseases like gout, hidradenitis suppurativa, recurrent pericarditis, and chronic recurrent multifocal osteomyelitis (CRMO), demonstrating a high degree of mechanistic convergence. Therapeutic strategies targeting IL-1 have shown favorable efficacy and safety in multiple clinical studies, with several agents approved for corresponding indications. As molecular mechanisms are further elucidated and biologic therapies continue to evolve, the IL-1 axis is increasingly recognized as a common inflammatory nexus within IMIDs. The reclassification framework centered on IL-1 provides a conceptual basis for the implementation of shared-treatment strategies across distinct diseases and establishes a theoretical and practical foundation for precision-targeted interventions.</abstract><keywords/></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Broderick L, Hoffman H, 2022. IL-1 and Autoinflammatory Disease: Biology, Pathogenesis and Therapeutic Targeting. Nat Rev Rheumatol, 18(8): 448–463.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B2" content-type="article"><label>2</label><element-citation publication-type="journal"><p>Shi L, Song L, Maurer K, et al., 2020. IL-1 Transcriptional Responses to Lipopolysaccharides Are Regulated by a Complex of RNA Binding Proteins. J Immunol, 204(5): 1334–1344.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B3" content-type="article"><label>3</label><element-citation publication-type="journal"><p>Sneezum L, Eislmayr K, Dworak H, et al., 2020. Context-Dependent IL-1 mRNA-Destabilization by TTP Prevents Dysregulation of Immune Homeostasis Under Steady State Conditions. Front Immunol, 11: 1398.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B4" content-type="article"><label>4</label><element-citation publication-type="journal"><p>Dagvadorj J, Mikulska-Ruminska K, Tumurkhuu G, et al., 2021. Recruitment of Pro-IL-1α to Mitochondrial Cardiolipin, via Shared LC3 Binding Domain, Inhibits Mitophagy and Drives Maximal NLRP3 Activation. Proc Natl Acad Sci U S A, 118(1), e2015632118.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B5" content-type="article"><label>5</label><element-citation publication-type="journal"><p>Bachetti T, Chiesa S, Castagnola P, et al., 2013. Autophagy Contributes to Inflammation in Patients with TNFR-Associated Periodic Syndrome (TRAPS). Ann Rheum Dis, 72(6): 1044–1052.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B6" content-type="article"><label>6</label><element-citation publication-type="journal"><p>Lopalco G, Rigante D, Vitale A, et al., 2015. Tumor Necrosis Factor Receptor-Associated Periodic Syndrome Managed with the Couple Canakinumab–Alendronate. Clin Rheumatol, 34(4): 807–809.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B7" content-type="article"><label>7</label><element-citation publication-type="journal"><p>Ter Haar N, Lachmann H, Özen S, et al., 2013. Treatment of Autoinflammatory Diseases: Results from the Eurofever Registry and a Literature Review. Ann Rheum Dis, 72(5): 678–685.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B8" content-type="article"><label>8</label><element-citation publication-type="journal"><p>Aksentijevich I, Masters S, Ferguson P, et al., 2009. An Autoinflammatory Disease with Deficiency of the Interleukin-1-Receptor Antagonist. N Engl J Med, 360(23): 2426–2437.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B9" content-type="article"><label>9</label><element-citation publication-type="journal"><p>Jesus A, Osman M, Silva C, et al., 2011. A Novel Mutation of IL1RN in the Deficiency of Interleukin-1 Receptor Antagonist Syndrome: Description of Two Unrelated Cases from Brazil. Arthritis Rheum, 63(12): 4007–4017.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B10" content-type="article"><label>10</label><element-citation publication-type="journal"><p>Reddy S, Jia S, Geoffrey R, et al., 2009. An Autoinflammatory Disease Due to Homozygous Deletion of the IL1RN Locus. N Engl J Med, 360(23): 2438–2444.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B11" content-type="article"><label>11</label><element-citation publication-type="journal"><p>Stenerson M, Dufendach K, Aksentijevich I, et al., 2011. The First Reported Case of Compound Heterozygous IL1RN Mutations Causing Deficiency of the Interleukin-1 Receptor Antagonist. Arthritis Rheum, 63(12): 4018–4022.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B12" content-type="article"><label>12</label><element-citation publication-type="journal"><p>Reginato A, Mount D, Yang I, et al., 2012. The Genetics of Hyperuricaemia and Gout. Nat Rev Rheumatol, 8(10): 610–621.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B13" content-type="article"><label>13</label><element-citation publication-type="journal"><p>Okada Y, Sim X, Go M, et al., 2012. Meta-Analysis Identifies Multiple Loci Associated with Kidney Function-Related Traits in East Asian Populations. Nat Genet, 44(8): 904–909.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B14" content-type="article"><label>14</label><element-citation publication-type="journal"><p>Tin A, Woodward O, Kao W, et al., 2011. Genome-Wide Association Study for Serum Urate Concentrations and Gout among African Americans Identifies Genomic Risk Loci and a Novel URAT1 Loss-of-Function Allele. Hum Mol Genet, 20(20): 4056–4068.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B15" content-type="article"><label>15</label><element-citation publication-type="journal"><p>Ombrello M, Arthur V, Remmers E, et al., 2017. Genetic Architecture Distinguishes Systemic Juvenile Idiopathic Arthritis from Other Forms of Juvenile Idiopathic Arthritis: Clinical and Therapeutic Implications. Ann Rheum Dis, 76(5): 906–913.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B16" content-type="article"><label>16</label><element-citation publication-type="journal"><p>Rabionet R, Remesal A, Mensa-Vilaró A, et al., 2019. Biallelic Loss-of-Function LACC1/FAMIN Mutations Presenting as Rheumatoid Factor-Negative Polyarticular Juvenile Idiopathic Arthritis. Sci Rep, 9(1): 4579.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B17" content-type="article"><label>17</label><element-citation publication-type="journal"><p>Cox A, Darbro B, Laxer R, et al., 2017. Recessive Coding and Regulatory Mutations in FBLIM1 Underlie the Pathogenesis of Chronic Recurrent Multifocal Osteomyelitis (CRMO). PLoS One, 12(3): e0169687.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B18" content-type="article"><label>18</label><element-citation publication-type="journal"><p>Grosse J, Chitu V, Marquardt A, et al., 2006. Mutation of Mouse Mayp/Pstpip2 Causes a Macrophage Autoinflammatory Disease. Blood, 107(8): 3350–3358.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B19" content-type="article"><label>19</label><element-citation publication-type="journal"><p>Ferguson P, Bing X, Vasef M, et al., 2006. A Missense Mutation in Pstpip2 Is Associated with the Murine Autoinflammatory Disorder Chronic Multifocal Osteomyelitis. Bone, 38(1): 41–47.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B20" content-type="article"><label>20</label><element-citation publication-type="journal"><p>Ferguson P, Chen S, Tayeh M, et al., 2005. Homozygous Mutations in LPIN2 Are Responsible for the Syndrome of Chronic Recurrent Multifocal Osteomyelitis and Congenital Dyserythropoietic Anaemia (Majeed Syndrome). J Med Genet, 42(7): 551–557.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B21" content-type="article"><label>21</label><element-citation publication-type="journal"><p>Wang B, Yang W, Wen W, et al., 2010. Gamma-Secretase Gene Mutations in Familial Acne Inversa. Science, 330(6007): 1065.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B22" content-type="article"><label>22</label><element-citation publication-type="journal"><p>Kees S, Langevitz P, Zemer D, et al., 1997. Attacks of Pericarditis as a Manifestation of Familial Mediterranean Fever (FMF). QJM, 90(10): 643–647.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B23" content-type="article"><label>23</label><element-citation publication-type="journal"><p>Brucato A, Shinar Y, Brambilla G, et al., 2005. Idiopathic Recurrent Acute Pericarditis: Familial Mediterranean Fever Mutations and Disease Evolution in a Large Cohort of Caucasian Patients. Lupus, 14(9): 670–674.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B24" content-type="article"><label>24</label><element-citation publication-type="journal"><p>Schlesinger N, Pillinger M, Simon L, et al., 2023. Interleukin-1β Inhibitors for the Management of Acute Gout Flares: A Systematic Literature Review. Arthritis Res Ther, 25(1): 128.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B25" content-type="article"><label>25</label><element-citation publication-type="journal"><p>Nordström D, Knight A, Luukkainen R, et al., 2012. Beneficial Effect of Interleukin 1 Inhibition with Anakinra in Adult-Onset Still’s Disease: An Open, Randomized, Multicenter Study. J Rheumatol, 39(10): 2008–2011.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B26" content-type="article"><label>26</label><element-citation publication-type="journal"><p>Ohlsson V, Baildam E, Foster H, et al., 2008. Anakinra Treatment for Systemic Onset Juvenile Idiopathic Arthritis (SOJIA). Rheumatology (Oxford), 47(4): 555–556.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B27" content-type="article"><label>27</label><element-citation publication-type="journal"><p>Gattorno M, Piccini A, Lasigliè D, et al., 2008. The Pattern of Response to Anti-Interleukin-1 Treatment Distinguishes Two Subsets of Patients with Systemic-Onset Juvenile Idiopathic Arthritis. Arthritis Rheum, 58(5): 1505–1515.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B28" content-type="article"><label>28</label><element-citation publication-type="journal"><p>Petryna O, Cush J, Efthimiou P, 2012. IL-1 Trap Rilonacept in Refractory Adult-Onset Still’s Disease. Ann Rheum Dis, 71(12): 2056–2057.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B29" content-type="article"><label>29</label><element-citation publication-type="journal"><p>Ilowite N, Prather K, Lokhnygina Y, et al., 2014. Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis. Arthritis Rheumatol, 66(9): 2570–2579.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B30" content-type="article"><label>30</label><element-citation publication-type="journal"><p>Ruperto N, Brunner H, Quartier P, et al., 2012. Two Randomized Trials of Canakinumab in Systemic Juvenile Idiopathic Arthritis. N Engl J Med, 367(25): 2396–2406.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B31" content-type="article"><label>31</label><element-citation publication-type="journal"><p>Kedor C, Listing J, Zernicke J, et al., 2020. Canakinumab for Treatment of Adult-Onset Still’s Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER): Phase II, Randomised, Double-Blind, Placebo-Controlled, Multicentre, Investigator-Initiated Trial. Ann Rheum Dis, 79(8): 1090–1097.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B32" content-type="article"><label>32</label><element-citation publication-type="journal"><p>Fautrel B, Mitrovic S, De Matteis A, et al., 2024. 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, 83(12): 1614–1627.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B33" content-type="article"><label>33</label><element-citation publication-type="journal"><p>Cox A, Zhao Y, Ferguson P, 2017. Chronic Recurrent Multifocal Osteomyelitis and Related Diseases—Update on Pathogenesis. Curr Rheumatol Rep, 19(4): 18.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B34" content-type="article"><label>34</label><element-citation publication-type="journal"><p>Scianaro R, Insalaco A, Laudiero L, et al., 2014. Deregulation of the IL-1β Axis in Chronic Recurrent Multifocal Osteomyelitis. Pediatr Rheumatol Online J, 12: 30.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B35" content-type="article"><label>35</label><element-citation publication-type="journal"><p>Acierno S, Angrisani F, Marino A, et al., 2022. Canakinumab Treatment in a Young Girl with Refractory Chronic Recurrent Multifocal Osteomyelitis Associated with Pyoderma Gangrenosum. Int J Rheum Dis, 25(11): 1333–1338.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B36" content-type="article"><label>36</label><element-citation publication-type="journal"><p>Twilt M, Laxer R, 2011. Clinical Care of Children with Sterile Bone Inflammation. Curr Opin Rheumatol, 23(5): 424–431.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B37" content-type="article"><label>37</label><element-citation publication-type="journal"><p>Witte-Händel E, Wolk K, Tsaousi A, et al., 2019. The IL-1 Pathway Is Hyperactive in Hidradenitis Suppurativa and Contributes to Skin Infiltration and Destruction. J Invest Dermatol, 139(6): 1294–1305.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B38" content-type="article"><label>38</label><element-citation publication-type="journal"><p>Molinelli E, Gioacchini H, Sapigni C, et al., 2023. New Insight into the Molecular Pathomechanism and Immunomodulatory Treatments of Hidradenitis Suppurativa. Int J Mol Sci, 24(9).</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B39" content-type="article"><label>39</label><element-citation publication-type="journal"><p>Tzanetakou V, Kanni T, Giatrakou S, et al., 2016. Safety and Efficacy of Anakinra in Severe Hidradenitis Suppurativa: A Randomized Clinical Trial. JAMA Dermatol, 152(1): 52–59.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B40" content-type="article"><label>40</label><element-citation publication-type="journal"><p>Lopalco G, Rigante D, Cantarini L, et al., 2021. The Autoinflammatory Side of Recurrent Pericarditis: Enlightening the Pathogenesis for a More Rational Treatment. Trends Cardiovasc Med, 31(5): 265–274.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B41" content-type="article"><label>41</label><element-citation publication-type="journal"><p>Denicolai M, Morello M, Golino M, et al., 2024. Interleukin-1 Blockade in Patients with ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity. J Cardiovasc Pharmacol, 10: 1097</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B42" content-type="article"><label>42</label><element-citation publication-type="journal"><p>Brucato A, Imazio M, Gattorno M, et al., 2016. Effect of Anakinra on Recurrent Pericarditis Among Patients with Colchicine Resistance and Corticosteroid Dependence: The AIRTRIP Randomized Clinical Trial. JAMA, 316(18): 1906–1912.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B43" content-type="article"><label>43</label><element-citation publication-type="journal"><p>Tabor E, 2021. Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis. N Engl J Med, 384(15): 1474.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B44" content-type="article"><label>44</label><element-citation publication-type="journal"><p>Epçaçan S, Sahin S, Kasapcopur O, 2019. Anaphylactic Reaction to Anakinra in a Child with Steroid-Dependent Idiopathic Recurrent Pericarditis and Successful Management with Canakinumab. Cardiol Young, 29(4): 549–551.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B45" content-type="article"><label>45</label><element-citation publication-type="journal"><p>Kougkas N, Fanouriakis A, Papalopoulos I, et al., 2018. Canakinumab for Recurrent Rheumatic Disease Associated-Pericarditis: A Case Series with Long-Term Follow-Up. Rheumatology (Oxford), 57(8): 1494–1495.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B46" content-type="article"><label>46</label><element-citation publication-type="journal"><p>Di Matteo A, Bathon J, Emery P, 2023. Rheumatoid Arthritis. Lancet, 402(10416): 2019–2033.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B47" content-type="article"><label>47</label><element-citation publication-type="journal"><p>Tak P, Bresnihan B, 2000. The Pathogenesis and Prevention of Joint Damage in Rheumatoid Arthritis: Advances from Synovial Biopsy and Tissue Analysis. Arthritis Rheum, 43(12): 2619–2633.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B48" content-type="article"><label>48</label><element-citation publication-type="journal"><p>Cohen S, Woolley J, Chan W, 2003. Interleukin 1 Receptor Antagonist Anakinra Improves Functional Status in Patients with Rheumatoid Arthritis. J Rheumatol, 30(2): 225–231.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B49" content-type="article"><label>49</label><element-citation publication-type="journal"><p>Cohen S, Moreland L, Cush J, et al., 2004. A Multicentre, Double Blind, Randomised, Placebo Controlled Trial of Anakinra (Kineret), a Recombinant Interleukin 1 Receptor Antagonist, in Patients with Rheumatoid Arthritis Treated with Background Methotrexate. Ann Rheum Dis, 63(9): 1062–1068.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B50" content-type="article"><label>50</label><element-citation publication-type="journal"><p>Bao J, Yue T, Liu W, et al., 2011. Secondary Failure to Treatment with Recombinant Human IL-1 Receptor Antagonist in Chinese Patients with Rheumatoid Arthritis. Clin Rheumatol, 30(5): 697–701.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B51" content-type="article"><label>51</label><element-citation publication-type="journal"><p>Nuki G, Bresnihan B, Bear M, et al., 2002. Long-Term Safety and Maintenance of Clinical Improvement Following Treatment with Anakinra (Recombinant Human Interleukin-1 Receptor Antagonist) in Patients with Rheumatoid Arthritis: Extension Phase of a Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheum, 46(11): 2838–2846.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B52" content-type="article"><label>52</label><element-citation publication-type="journal"><p>Alten R, Gomez-Reino J, Durez P, et al., 2011. Efficacy and Safety of the Human Anti-IL-1β Monoclonal Antibody Canakinumab in Rheumatoid Arthritis: Results of a 12-Week, Phase II, Dose-Finding Study. BMC Musculoskelet Disord, 12: 153.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B53" content-type="article"><label>53</label><element-citation publication-type="journal"><p>National Clinical Research Center for Dermatologic and Immunologic Diseases (Peking Union Medical College Hospital), Chinese Rheumatology Association, Rehabilitation Professional Committee of Rheumatology and Immunology of Chinese Association of Rehabilitation Medicine, et al., 2024. Chinese Guidelines for the Diagnosis and Treatment of Rheumatoid Arthritis. Chinese Journal of Internal Medicine, 63(11): 1059–1077.</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
