IL-1 pathways in inflammation and human diseases

Gabay, Cem; Lamacchia, Céline; Palmer, Gaby

doi:10.1038/nrrheum.2010.4

Cited by 897Inflammasome and immune disordersImmune Response and InflammationAutoimmune and Inflammatory Disorders Research

IL-1 pathways in inflammation and human diseases

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Gabay, Cem, Lamacchia, Céline, Palmer, Gaby·2010·Nature Reviews Rheumatology

DOI 10.1038/nrrheum.2010.4

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Abstract

Interleukin (IL)-1 was first cloned in the 1980s, and rapidly emerged as a key player in the regulation of inflammatory processes. The term IL-1 refers to two cytokines, IL-1alpha and IL-1beta, which are encoded by two separate genes. The effects of IL-1 are tightly controlled by several naturally occurring inhibitors, such as IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type II (IL-1RII), and other soluble receptors. Numerous IL-1 inhibitors have been developed and tested primarily in rheumatoid arthritis, with only modest effects. By contrast, the use of IL-1 antagonists has been uniformly associated with beneficial effects in patients with hereditary autoinflammatory conditions associated with excessive IL-1 signaling, such as cryopyrinopathies and IL-1Ra deficiency. Successful treatment with IL-1 blockers has also been reported in other hereditary autoinflammatory diseases, as well as in nonhereditary inflammatory diseases, such as Schnizler syndrome, systemic-onset juvenile idiopathic arthritis and adult Still disease. The role of microcrystals in the regulation of IL-1beta processing and release has provided the rationale for the use of IL-1 inhibitors in crystal-induced arthritis. Finally, preliminary results indicating that IL-1 targeting is efficacious in type 2 diabetes and smoldering myeloma have further broadened the spectrum of IL-1-driven diseases.

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Early microglial changes included significant upregulation of gene sets involved in inflammatory processes, interferon response, Fc receptors, MHC class II components, and complement components.
“Early changes included significant upregulation of gene sets involved in inflammatory processes (IL1B, CSF1R, STAB1, NINJ1, JAK3)61–65, interferon response (IRF1, IRF7, IFI16), Fc receptors (FCGR1A, FCGR1B, FCGR2A, FCGR3B), components of the class II major histocompatibility complex (MHC) (CD74, HLA-DRB5) and complement components (C1QA, C1QB) (Fig. 6d, top, red).”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [61]
IL-1 has a crucial role in sterile inflammatory responses.
“Given the crucial role for IL-1 in sterile inflammatory responses, blockade of IL-1R has been tested as a therapeutic target for sterile inflammatory disorders in humans.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [43]
IL-1R antagonism in other inflammatory joint diseases such as osteoarthritis and rheumatoid arthritis has shown little or no clinical benefit in human clinical trials.
“However, the effect of IL-1R antagonism in other inflammatory joint diseases, such as osteoarthritis and rheumatoid arthritis, has not been as promising, with little or no clinical benefit shown in human clinical trials43.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [43]

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Authors: Gabay, C., Lamacchia, C., & Palmer, G.
Affiliations: University of Geneva (CH)
Corresponding author: Gabay, Cem
ORCID: Gabay, Cem
Lamacchia, Céline
Palmer, Gaby
Venue: Nature Reviews Rheumatology
Publisher: Springer Science and Business Media LLC
Published: 2010-02-23
Volume: 6
Issue: 4
Pages: 232-241
ISSN: 1759-4790 (ISSN-L)
1759-4804
DOI: 10.1038/nrrheum.2010.4
OpenAlex: W1986843662
Cited by: 897
References: 116
Citations by year: 2026: 45 · 2025: 64 · 2024: 81 · 2023: 82 · 2022: 90 · 2021: 68 · 2020: 56 · 2019: 44 · 2018: 41 · 2017: 36 · 2016: 28 · 2015: 47 · 2014: 55 · 2013: 45 · 2012: 51
FWCI: 4.48
Type: journal article
Language: en
Open access: green
archive-ouverte.unige.ch
Licence: cc-by
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Rheumatology (publishedVersion)
PubMed (publishedVersion)
Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords: interleukin-1, IL-1α, IL-1β, interleukin-1 receptor antagonist, IL-1 inhibitors, hereditary autoinflammatory disease, cryopyrinopathies, systemic juvenile idiopathic arthritis, adult-onset Still's disease, crystal arthropathy, IL-1β processing, type 2 diabetes, smoldering multiple myeloma, inflammation
MeSH terms: Animals, Disease Models, Animal, Female, Humans, Inflammation, Interleukin-1, Male, Prognosis, Rheumatic Diseases, Cohort Studies, Signal Transduction, Drug Delivery Systems, Treatment Outcome, Receptors, Interleukin, Risk Assessment, Inflammation Mediators, Mice, Interleukin-1beta, Interleukin 1 Receptor Antagonist Protein

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