The DOI matches its Crossref record; 160 of the 165 references it cites were found in a registry or an index.
Interleukin-18, more than a Th1 cytokine
Abstract
Together with IL-12 or IL-15, interleukin-18 (IL-18) plays a major role in the production of interferon-γ from T-cells and natural killer cells; thus, IL-18 is considered to have a major role in the Th1 response. However, without IL-12, IL-18 is proinflammatory in an IFNγ independent manner. IL-18 is a member of the IL-1 family of cytokines and similar to IL-1β, the cytokine is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine. IL-18 is also present as an integral membrane protein but requires caspase-1 for full activity in order to induce IFNγ. Uniquely, unlike IL-1β, the IL-18 precursor is constitutively present in nearly all cells in healthy humans and animals. The activity of IL-18 is balanced by the presence of a high-affinity, naturally occurring IL-18 binding protein (IL-18BP). In humans, increased disease severity can be associated with an imbalance of IL-18 to IL-18BP such that the levels of free IL-18 are elevated in the circulation. Increasing number of studies have expanded the role of IL-18 in mediating inflammation in animal models of disease using the IL-18BP, IL-18 deficient mice, neutralization of IL-18 or deficiency in the IL-18 receptor alpha chain. A role for IL-18 has been implicated in several autoimmune diseases, myocardial function, emphysema, metabolic syndromes, psoriasis, inflammatory bowel disease, macrophage activation syndrome, sepsis and acute kidney injury, although paradoxically, in some models of disease, IL-18 is protective. The IL-18BP has been used safely in humans and clinical trials of IL-18BP as well as neutralizing anti-IL-18 antibodies are being tested in various diseases.
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“The ratio of free interleukin-18 to bound interleukin-18–IL18BP complexes in serum is an important indicator of the severity of the macrophage activation syndrome.44,47”
From Cytokine storm (2020) · cites this paper as [47]
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Cited by
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Fajgenbaum, D. C., & June, C. H. (2020) · New England Journal of Medicine · doi:10.1056/nejmra2026131 · Cited by 3,196
Canna, S., de Jesus, A. A., Gouni, S., Brooks, S. R., Marrero, B., Liu, Y., DiMattia, M. A., Zaal, K. J. M., Sanchez, G. A. M., Kim, H., et al. (2014) · Nature Genetics · doi:10.1038/ng.3089 · Cited by 747
Interleukin‐18: Biological properties and role in disease pathogenesis
Kaplanski, G. (2017) · Immunological Reviews · doi:10.1111/imr.12616 · Cited by 621
Self-citationGerfaud‐Valentin, M., Jamilloux, Y., Iwaz, J., & Sève, P. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2014.01.058 · Cited by 526
Proteolytic Processing of Interleukin-1 Family Cytokines: Variations on a Common Theme
Afonina, I. S., Müller, C., Martin, S. J., & Beyaert, R. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.003 · Cited by 483
Metadata
- Authors
- Novick, D., Kim, S., Kaplanski, G., & Dinarello, C. A.
- Affiliations
- Weizmann Institute of Science (IL)
- Konkuk University (KR)
- Aix-Marseille Université (FR)
- University of Colorado Denver (US)
- Corresponding author
- Dinarello, Charles A.
- Venue
- Seminars in Immunology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 25
- Issue
- 6
- Pages
- 439-448
- ISSN
- 1044-5323 (ISSN-L)
- OpenAlex
- W2005242977
- Cited by
- 280
- References
- 165
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 16 · 2023: 23 · 2022: 20 · 2021: 23 · 2020: 36 · 2019: 21 · 2018: 29 · 2017: 28 · 2016: 35 · 2015: 20 · 2014: 9
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- National Cancer Institute (CA 046934, P30CA046934)
- National Institute of Allergy and Infectious Diseases (AI‑15614)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR‑45584, R01AR045584)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-18, IL-18BP, Th1 response, interferon-gamma, IL-18 receptor alpha, IL-1 family cytokines, pro-inflammatory effects, autoimmune disease, macrophage activation syndrome, sepsis, acute kidney injury
- MeSH terms
- Animals, Autoimmune Diseases, Heart Diseases, Humans, Inflammation, Interferon-gamma, Killer Cells, Natural, Shock, Septic, Th1 Cells, Interleukin-12, Inflammation Mediators, Caspase 1, Interleukin-18, Intercellular Signaling Peptides and Proteins, Mice, Macrophage Activation Syndrome
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