Cited by 3,466Immune Response and InflammationInflammasome and immune disordersCytokine Signaling Pathways and Interactions

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Immunological and Inflammatory Functions of the Interleukin-1 Family

Dinarello, Charles A.·2009·Annual Review of Immunology

DOI 10.1146/annurev.immunol.021908.132612

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Abstract

More than any other cytokine family, the interleukin (IL)-1 family is closely linked to the innate immune response. This linkage became evident upon the discovery that the cytoplasmic domain of the IL-1 receptor type I is highly homologous to the cytoplasmic domains of all Toll-like receptors (TLRs). Thus, fundamental inflammatory responses such as the induction of cyclooxygenase type 2, increased expression of adhesion molecules, or synthesis of nitric oxide are indistinguishable responses of both IL-1 and TLR ligands. Both families nonspecifically affect antigen recognition and lymphocyte function. IL-1beta is the most studied member of the IL-1 family because of its role in mediating autoinflammatory diseases. Although the TLR and IL-1 families evolved to assist in host defense against infection, unlike the TLR family, the IL-1 family also includes members that suppress inflammation, both specifically within the IL-1 family but also nonspecifically for TLR ligands and the innate immune response.

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IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions
Konishi, H., Tsutsui, H., Murakami, T., Futatsugi‐Yumikura, S., Yamanaka, K.-I., Tanaka, M., Iwakura, Y., 昇, 鈴., Takeda, K., Akira, S., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152337799 · Cited by 269
Caspase-1-dependent processing of pro-interleukin-1β is cytosolic and precedes cell death
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ATP Acts as an Agonist to Promote Stimulus-Induced Secretion of IL-1β and IL-18 in Human Blood
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Intestinal inflammation in mice deficient in Tir8 , an inhibitory member of the IL-1 receptor family
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A complex of the IL-1 homologue IL-1F7b and IL-18-binding protein reduces IL-18 activity
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Pattern of interleukin‐1β secretion in response to lipopolysaccharide and ATP before and after interleukin‐1 blockade in patients with CIAS1 mutations
Gattorno, M., Tassi, S., Carta, S., Delfino, L., Ferlito, F., Pelagatti, M. A., D’Osualdo, A., Buoncompagni, A., Alpigiani, M. G., Alessio, M., et al. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22842 · Cited by 247
Caspase-1-Independent, Fas/Fas Ligand–Mediated IL-18 Secretion from Macrophages Causes Acute Liver Injury in Mice
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The IL-1 Family Member 7b Translocates to the Nucleus and Down-Regulates Proinflammatory Cytokines
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The IL-1 Receptor-Related T1 Antigen Is Expressed on Immature and Mature Mast Cells and on Fetal Blood Mast Cell Progenitors
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Response to local inflammation of IL-1 beta-converting enzyme- deficient mice
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Dissociation between interleukin-1 beta mRNA and protein synthesis in human peripheral blood mononuclear cells.
Schindler, R., Clark, B. D., & Dinarello, C. A. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)86936-8 · Cited by 228
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SIGIRR Inhibits Interleukin-1 Receptor- and Toll-like Receptor 4-mediated Signaling through Different Mechanisms
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IL-1Rrp Is a Novel Receptor-like Molecule Similar to the Type I Interleukin-1 Receptor and Its Homologues T1/ST2 and IL-1R AcP
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Cloning and Characterization of IL-1HY2, a Novel Interleukin-1 Family Member
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Potentiation of Caspase-1 Activation by the P2X7 Receptor Is Dependent on TLR Signals and Requires NF-κB-Driven Protein Synthesis
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SOCS-3 negatively regulates innate and adaptive immune mechanisms in acute IL-1-dependent inflammatory arthritis
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T1/ST2 Signaling Establishes It as a Member of an Expanding Interleukin-1 Receptor Family
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IL-1H, AN INTERLEUKIN 1-RELATED PROTEIN THAT BINDS IL-18 RECEPTOR/IL-1Rrp
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Interleukin-1 induces interleukin-8 secretion from endothelial cells by a juxtacrine mechanism
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MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever
Livneh, A., Langevitz, P., Shinar, Y., Zaks, N., Kastner, D. L., Pras, M., & Pras, E. (1999) · Amyloid · doi:10.3109/13506129908993281 · Cited by 201
Therapeutic strategies to reduce IL-1 activity in treating local and systemic inflammation
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Effect of endotoxin in IL-1 β-deficient mice
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IL-12–induced IFN-γ is dependent on caspase-1 processing of the IL-18 precursor
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Identification and Gene Organization of Three Novel Members of the IL-1 Family on Human Chromosome 2
Busfield, S. J., Comrack, C. A., Yu, G., Chickering, T. W., Smutko, J. S., Zhou, H., Leiby, K. R., Holmgren, L. M., Gearing, D. P., & Pan, Y. (2000) · Genomics · doi:10.1006/geno.2000.6184 · Cited by 173
IL-1 Receptor Accessory Protein Is an Essential Component of the IL-1 Receptor
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Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency
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A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST2
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Interleukin-1 homologues IL-1F7b and IL-18 contain functional mRNA instability elements within the coding region responsive to lipopolysaccharide
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Interleukin 18–independent engagement of interleukin 18 receptor-α is required for autoimmune inflammation
Gutcher, I., Urich, E., Wolter, K., Prinz, M., & Becher, B. (2006) · Nature Immunology · doi:10.1038/ni1377 · Cited by 161
Glu496 to Ala Polymorphism in the P2X7 Receptor Impairs ATP-Induced IL-1β Release from Human Monocytes
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Interleukin‐1β, but not interleukin‐1α, is required for T‐cell‐dependent antibody production
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Mechanisms of Inhibition of Collagen-Induced Arthritis by Murine IL-18 Binding Protein
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The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synovial fibroblasts and articular chondrocytes
Magne, D., Palmer, G., Barton, J. L., Mézin, F., Talabot‐Ayer, D., Bas, S., Duffy, T., Noger, M., Guerne, P., Nicklin, M. J. H., et al. (2006) · Arthritis Research & Therapy · doi:10.1186/ar1946 · Cited by 146
Glucose- and Interleukin-1β-Induced β-Cell Apoptosis Requires Ca2+ Influx and Extracellular Signal-Regulated Kinase (ERK) 1/2 Activation and Is Prevented by a Sulfonylurea Receptor 1/Inwardly Rectifying K+ Channel 6.2 (SUR/Kir6.2) Selective Potassium Channel Opener in Human Islets
Maedler, K., Størling, J., Sturis, J., Zuellig, R. A., Spinas, G. A., Arkhammar, P. O. G., Mandrup-Poulsen, T. R., & Donath, M. Y. (2004) · Diabetes · doi:10.2337/diabetes.53.7.1706 · Cited by 146
HMG-1 REDISCOVERED AS A CYTOKINE
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Identification of a Novel Human Cytokine Gene in the Interleukin Gene Cluster on Chromosome 2q12-14
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Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes
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A short synthetic peptide fragment of human interleukin 1 with immunostimulatory but not inflammatory activity.
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Cutting Edge: IL-18-Transgenic Mice: In Vivo Evidence of a Broad Role for IL-18 in Modulating Immune Function
Hoshino, T., Kawase, Y., Okamoto, M., Yokota, K., Yoshino, K., Yamamura, K., Miyazaki, J., Young, H. A., & Ōizumi, K. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.12.7014 · Cited by 135
The Interleukin‐1 Receptor Family
Boraschi, D., & Tagliabue, A. (2006) · Vitamins & Hormones · doi:10.1016/s0083-6729(06)74009-2 · Cited by 133
Abnormal T cell activation caused by the imbalance of the IL-1/IL-1R antagonist system is responsible for the development of experimental autoimmune encephalomyelitis
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Endogenous interleukin 1 alpha must be transported to the nucleus to exert its activity in human endothelial cells.
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Resistant Behçet Disease Responsive to Anakinra
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IL-1 induces IL-1. IV. IFN-gamma suppresses IL-1 but not lipopolysaccharide-induced transcription of IL-1.
Schindler, R., Ghezzi, P., & Dinarello, C. A. (1990) · The Journal of Immunology · doi:10.4049/jimmunol.144.6.2216 · Cited by 129
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Interleukin-1 receptor antagonist in normal and psoriatic epidermis.
Hammerberg, C., Arend, W. P., Fisher, G. J., Chan, L. S., Berger, A. E., Haskill, J. S., Voorhees, J. J., & Cooper, K. D. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115896 · Cited by 126
A Key Role for Redox Signaling in Rapid P2X7 Receptor-Induced IL-1β Processing in Human Monocytes
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IFN-γ-Dependent and -Independent Mechanisms in Adverse Effects Caused by Concomitant Administration of IL-18 and IL-12
Nakamura, S., Otani, T., Ijiri, Y., Motoda, R., Kurimoto, M., & Orita, K. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.6.3330 · Cited by 113
The N-terminal propiece of interleukin 1α is a transforming nuclear oncoprotein
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Differential role and tissue specificity of interleukin-1α gene expression in atherogenesis and lipid metabolism
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The many worlds of reducing interleukin‐1
Dinarello, C. A. (2005) · Arthritis & Rheumatism · doi:10.1002/art.21107 · Cited by 104
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Recombinant human interleukin‐1 receptor type I in the treatment of patients with active rheumatoid arthritis
Drevlow, B. E., Lovis, R. M., Haag, M. A., Sinacore, J. M., Jacobs, C. A., Blosche, C., LANDAY, A. L., Moreland, L. W., & Pope, R. M. (1996) · Arthritis & Rheumatism · doi:10.1002/art.1780390212 · Cited by 103
P2X7 receptor polymorphism impairs extracellular adenosine 5′-triphosphate-induced interleukin-18 release from human monocytes
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IL1HY1: A Novel Interleukin-1 Receptor Antagonist Gene
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Prevention of IL-1 signaling attenuates airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate–induced asthma
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Innate Immunity Mediated by the Cytokine IL-1 Homologue 4 (IL-1H4/IL-1F7) Induces IL-12-Dependent Adaptive and Profound Antitumor Immunity
Gao, W., Kumar, S., Lotze, M. T., Hanning, C. R., Robbins, P. D., & Gambotto, A. A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.1.107 · Cited by 93
Pharmacokinetics of IL-18 binding protein in healthy volunteers and subjects with rheumatoid arthritis or plaque psoriasis
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Functional Reconstitution and Regulation of IL-18 Activity by the IL-18Rβ Chain
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Intracellular IL-1α-binding proteins contribute to biological functions of endogenous IL-1α in systemic sclerosis fibroblasts
Kawaguchi, Y., Nishimagi, E., Tochimoto, A., Kawamoto, M., Katsumata, Y., Soejima, M., Kanno, T., Kamatani, N., & Hara, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603545103 · Cited by 85
Development of a Novel Noncompetitive Antagonist of IL-1 Receptor
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SIGIRR Promotes Resistance against Pseudomonas aeruginosa Keratitis by Down-Regulating Type-1 Immunity and IL-1R1 and TLR4 Signaling
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IL‐1F5 mediates anti‐inflammatory activity in the brain through induction of IL‐4 following interaction with SIGIRR/TIR8
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Interleukin‐1 receptor accessory protein interacts with the type II interleukin‐1 receptor
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Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice
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The Membrane Form of the Type II IL-1 Receptor Accounts for Inhibitory Function
Neumann, D., Kollewe, C., Martin, M. U., & Boraschi, D. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.6.3350 · Cited by 77
Peripheral blood mononuclear cells stimulated with C5a or lipopolysaccharide to synthesize equivalent levels of IL-1 beta mRNA show unequal IL-1 beta protein accumulation but similar polyribosome profiles.
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Correspondence of the Functional Epitopes of Poxvirus and Human Interleukin-18-Binding Proteins
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Cytokines in human renal interstitial fibrosis. II. Intrinsic interleukin (IL)-1 synthesis and IL-1-dependent production of IL-6 and IL-8 by cultured kidney fibroblasts
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Cutting Edge: IL-1 Controls the IL-23 Response Induced by Gliadin, the Etiologic Agent in Celiac Disease
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Identification of the promoter region of human interleukin 1 type I receptor gene: multiple initiation sites, high G+C content, and constitutive expression.
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Identification of Amino Acid Residues Critical for Biological Activity in Human Interleukin-18
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Mutations in cryopyrin: Bypassing roadblocks in the caspase 1 inflammasome for interleukin‐1β secretion and disease activity
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IL-33: A Sheep in Wolf’s Clothing?
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Soluble interleukin-1 receptor accessory protein ameliorates collagen-induced arthritis by a different mode of action from that of interleukin-1 receptor antagonist.
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Antiviral and immunoregulatory activities of IFN-γ depend on constitutively expressed IL-1α
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Phosphorylation of IRF8 in a pre-associated complex with Spi-1/PU.1 and non-phosphorylated Stat1 is critical for LPS induction of the IL1B gene
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Responses of IL-18- and IL-18 receptor-deficient pancreatic islets with convergence of positive and negative signals for the IL-18 receptor
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Different patterns of interleukin-1alpha and interleukin-1beta expression in organs of normal young and old mice.
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Adenovirus expressing interleukin-1 receptor antagonist alleviates allergic airway inflammation in a murine model of asthma
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Protective Effect of IL-18 on Kainate- and IL-1β-Induced Cerebellar Ataxia in Mice
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EVIDENCE THAT HAX-1 IS AN INTERLEUKIN-1α N-TERMINAL BINDING PROTEIN
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See all 3,466

Authors: Dinarello, C. A.
Affiliations: University of Colorado Anschutz (US)
Corresponding author: Dinarello, Charles A.
ORCID: Dinarello, Charles A.
Venue: Annual Review of Immunology
Publisher: Annual Reviews
Published: 2009-04-01
Volume: 27
Issue: 1
Pages: 519-550
ISSN: 0732-0582 (ISSN-L)
1545-3278
DOI: 10.1146/annurev.immunol.021908.132612
OpenAlex: W2165275387
Cited by: 3,466
References: 170
Citations by year: 2026: 95 · 2025: 169 · 2024: 195 · 2023: 185 · 2022: 209 · 2021: 183 · 2020: 199 · 2019: 202 · 2018: 231 · 2017: 219 · 2016: 198 · 2015: 223 · 2014: 244 · 2013: 227 · 2012: 206
FWCI: 17.82
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (AI‑15614)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: interleukin-1 family, innate immunity, inflammation, Toll-like receptors, IL-1 receptor type I, IL-1β, autoinflammatory disease, adhesion molecules, nitric oxide, antigen recognition, lymphocyte function, anti-inflammatory cytokines
MeSH terms: NLR Family, Pyrin Domain-Containing 3 Protein, Animals, B-Lymphocytes, Carrier Proteins, T-Lymphocytes, Helper-Inducer, Humans, Immunity, Innate, Inflammation, Interleukin-1, Signal Transduction, Receptors, Interleukin-1, Receptors, Purinergic P2, Caspase 1, Toll-Like Receptors, Receptors, Purinergic P2X7

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Immunological and Inflammatory Functions of the Interleukin-1 Family

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