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Cited by 2,248Inflammasome and immune disordersImmune Response and InflammationCytokine Signaling Pathways and Interactions

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Interleukin-1 in the pathogenesis and treatment of inflammatory diseases

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Dinarello, Charles A.·2011·Blood
DOI 10.1182/blood-2010-07-273417PMC PMC3083294
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Abstract

More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors.

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Metadata

Authors
Dinarello, C. A.
Affiliations
Radboud University Nijmegen (NL)
Corresponding author
Dinarello, Charles A.
ORCID
Dinarello, Charles A.
Venue
Blood
Publisher
American Society of Hematology
Published
2011-04-07
Volume
117
Issue
14
Pages
3720-3732
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2010-07-273417
PMC
PMC3083294
OpenAlex
W2150107812
Cited by
2,248
References
118
Citations by year
2026: 138 · 2025: 173 · 2024: 151 · 2023: 150 · 2022: 161 · 2021: 160 · 2020: 159 · 2019: 164 · 2018: 151 · 2017: 145 · 2016: 123 · 2015: 154 · 2014: 139 · 2013: 124 · 2012: 110
FWCI
12.05
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • National Cancer Institute (CA 046934, P30CA046934)
  • National Institute of Allergy and Infectious Diseases (AI‑15614, R56AI015614, R01AI015614)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords
interleukin-1, IL-1 receptor family, innate immunity, autoinflammatory disease, autoimmune disease, caspase-1, gout, type 2 diabetes, rheumatoid arthritis, recurrent pericarditis, smoldering multiple myeloma, heart failure, anti-inflammatory therapy
MeSH terms
Animals, Autoimmune Diseases, Disease, Multigene Family, Humans, Inflammation, Interleukin-1, Models, Biological, Receptors, Interleukin-1, Toll-Like Receptors, Molecular Targeted Therapy

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