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Cited by 606

The DOI matches its Crossref record; 228 of the 228 references it cites were found in a registry or an index.

Interleukin‐18: Biological properties and role in disease pathogenesis

Open access
Kaplanski, Gilles·2018·Immunological Reviews

Abstract

Summary: Initially described as an interferon (IFN)γ‐inducing factor, interleukin (IL)‐18 is indeed involved in Th1 and NK cell activation, but also in Th2, IL‐17‐producing γδ T cells and macrophage activation. IL‐18, a member of the IL‐1 family, is similar to IL‐1β for being processed by caspase 1 to an 18 kDa‐biologically active mature form. IL‐18 binds to its specific receptor (IL‐18Rα, also known as IL‐1R7) forming a low affinity ligand chain. This is followed by recruitment of the IL‐18Rβ chain. IL‐18 then uses the same signaling pathway as IL‐1 to activate NF‐kB and induce inflammatory mediators such as adhesion molecules, chemokines and Fas ligand. IL‐18 also binds to the circulating high affinity IL‐18 binding protein (BP), such as only unbound free IL‐18 is active. IL‐18Rα may also bind IL‐37, another member of the IL‐1 family, but in association with the negative signaling chain termed IL‐1R8, which transduces an anti‐inflammatory signal. IL‐18 BP also binds IL‐37 and this acts as a sink for the anti‐inflammatory properties of IL‐37. There is now ample evidence for a role of IL‐18 in various infectious, metabolic or inflammatory diseases such as influenza virus infection, atheroma, myocardial infarction, chronic obstructive pulmonary disease, or Crohn's disease. However, IL‐18 plays a very specific role in the pathogenesis of hemophagocytic syndromes (HS) also termed Macrophage Activation Syndrome. In children affected by NLRC 4 gain‐of‐function mutations, IL‐18 circulates in the range of tens of nanograms/mL. HS is treated with the IL‐1 Receptor antagonist (anakinra) but also specifically with IL‐18 BP. Systemic juvenile idiopathic arthritis or adult‐onset Still's disease are also characterized by high serum IL‐18 concentrations and are treated by IL‐18BP.

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Metadata

Authors
Kaplanski, G.
Venue
Immunological Reviews
Publisher
Wiley
Published
2017-12-16
Volume
281
Issue
1
Pages
138-153
ISSN
  • 0105-2896 (ISSN-L)
  • 1600-065X
OpenAlex
W2781447571
Cited by
606
References
228
FWCI
3.89
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Interleukin‐18: Biological properties and role in disease pathogenesis. https://app.cochat.ai/papers/10.1111/imr.12616
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Kaplanski, G. (2018). Interleukin‐18: Biological properties and role in disease pathogenesis. Immunological Reviews. https://doi.org/10.1111/imr.12616

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