JCNRJournal of Clinical and Nursing Research2208-36852208-3693Bio-Byword Scientific Publishing Pty. Ltd.10.26689/jcnr.v10i5.15208ArticleExploring the Mechanistic Foundations of the Long-Term Safety of IL-1β Targeted Anti-Inflammatory Therapyhttps://artdesignp.com/journal/JCNR/10/5/10.26689/jcnr.v10i5.15208ChenMo,YuSen,WuHuaxiang,LiYi20261052026-05-31The expanding clinical use of interleukin-1β (IL-1β) monoclonal antibodies (mAbs) for chronic diseases raises important questions about their long-term safety, particularly infection risk. Despite IL-1β serves as a central driver of inflammatory responses, multiple large-scale clinical trials have demonstrated that specific blockade of IL-1β does not substantially increase overall infection risk in patients. This review explores the mechanistic basis for this favorable benefit‑risk profile. It highlights the constitutive immune mechanisms that provide a stable first line of defense independent of IL-1β induction, the high complementarity within the IL-1 family enabling selective blockade benefits, and the pharmacokinetic profiles of biologics ensuring selective lesion distribution. Furthermore, it discusses the precise neutralization of systemic spillover inflammation while preserving local autocrine/paracrine homeostasis, the evolving disease spectrum in which sterile inflammation has surpassed infection as a primary health challenge, and the need for clinical vigilance against specific pathogen infections. Overall, specific blockade of IL-1β achieves effective anti‑inflammatory therapy without compromising fundamental host defense.

Paludan S, Pradeu T, Masters S, et al., 2021, Constitutive Immune Mechanisms: Mediators of Host Defence and Immune Regulation. Nature Reviews Immunology, 21(3): 137–150.

Nish S, Medzhitov R, 2011, Host Defense Pathways: Role of Redundancy and Compensation in Infectious Disease Phenotypes. Immunity, 34(5): 629–636.

Garlanda C, Di Ceglie I, Jaillon S, 2025, IL-1 Family Cytokines in Inflammation and Immunity. Cellular & Molecular Immunology, 22(11): 1345–1362.

Bourigault M, Segueni N, Rose S, et al., 2013, Relative Contribution of IL-1α, IL-1β and TNF to the Host Response to Mycobacterium tuberculosis and Attenuated M. bovis BCG. Immunity, Inflammation and Disease, 1(1): 47–62.

Putnam N, Fulbright L, Curry J, et al., 2019, MyD88 and IL-1R Signaling Drive Antibacterial Immunity and Osteoclast-Driven Bone Loss During Staphylococcus aureus Osteomyelitis. PLoS Pathogens, 15(4): e1007744.

Eislmayr K, Bestehorn A, Morelli L, et al., 2022, Nonredundancy of IL-1α and IL-1β Is Defined by Distinct Regulation of Tissues Orchestrating Resistance Versus Tolerance to Infection. Science Advances, 8(9): eabj7293.

Bader S, Scherer L, Schaefer J, et al., 2025, IL-1β Drives SARS-CoV-2-Induced Disease Independently of the Inflammasome and Pyroptosis Signalling. Cell Death & Differentiation, 32(7): 1353–1366.

Bawazeer A, Rosli S, Harpur C, et al., 2021, Interleukin-1β Exacerbates Disease and Is a Potential Therapeutic Target to Reduce Pulmonary Inflammation During Severe Influenza A Virus Infection. Immunology & Cell Biology, 99(7): 737–748.

Chen X, DuBois D, Almon R, et al., 2015, Biodistribution of Etanercept to Tissues and Sites of Inflammation in Arthritic Rats. Drug Metabolism and Disposition, 43(6): 898–907.

Tabrizi M, Bornstein G, Suria H, 2010, Biodistribution Mechanisms of Therapeutic Monoclonal Antibodies in Health and Disease. AAPS Journal, 12(1): 33–43.

Lopez-Castejon G, Brough D, 2011, Understanding the Mechanism of IL-1β Secretion. Cytokine & Growth Factor Reviews, 22(4): 189–195.

Scanu A, Oliviero F, Ramonda R, et al., 2012, Cytokine Levels in Human Synovial Fluid During the Different Stages of Acute Gout: Role of Transforming Growth Factor β1 in the Resolution Phase. Annals of the Rheumatic Diseases, 71(4): 621–624.

Silvain J, Kerneis M, Zeitouni M, et al., 2020, Interleukin-1β and Risk of Premature Death in Patients with Myocardial Infarction. Journal of the American College of Cardiology, 76(15): 1763–1773.

GBD 2019 Diseases and Injuries Collaborators, 2020, Global Burden of 369 Diseases and Injuries in 204 Countries and Territories, 1990–2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet, 396(10258): 1204–1222.

Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017; 377(12):1119-1131.

Christ A, Günther P, Lauterbach M, et al., 2018, Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming. Cell, 172(1–2): 162–175.

Liesz A, 2026, Trained Immunity in Interorgan Communication and Vascular Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 46(3): e323130.

LaRock C, Todd J, LaRock D, et al., 2016, IL-1β Is an Innate Immune Sensor of Microbial Proteolysis. Science Immunology, 1(2): eaah3539.

Brouwer S, Rivera-Hernandez T, Curren B, et al., 2023, Pathogenesis, Epidemiology and Control of Group A Streptococcus Infection. Nature Reviews Microbiology, 21(7): 431–447.

Ridker P, Bhatt D, Nissen S, 2024, Inflammation, Infection, and Cardiovascular Risk—Authors’ Reply. Lancet, 403(10431): 1025–1026.

Li Y, Oosting M, Deelen P, et al., 2016, Inter-Individual Variability and Genetic Influences on Cytokine Responses to Bacteria and Fungi. Nature Medicine, 22(8): 952–960.