Interleukin-18 and IL-18 Binding Protein

By C. A. Dinarello, D. Novick, Soohyun Kim, G. Kaplanski. Frontiers in Immunology, 2013

866 citations recorded by the source corpus.

Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines. Similar to IL-1β, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine but 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, hemophagocytic syndromes, macrophage activation syndrome, sepsis, and acute kidney injury, although in some models of disease, IL-18 is protective. IL-18 plays a major role in the production of interferon-γ from T-cells and natural killer cells. The IL-18BP has been used safely in humans and clinical trials of IL-18BP as well as neutralizing anti-IL-18 antibodies are in clinical trials. This review updates the biology of IL-18 as well as its role in human disease.

Subfields: Hematology, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/ea0e0c39c59081fb5045c91bb8a9fd4ce874400c

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Citations in the corpus

• Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “IL-18’s multiple pro-inflammatory effects are modulated through IL-18 binding protein (166).”
• Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. (2019, background): “In general, genetic deficiency in, or the blockade of, IL1-β and IL-18 signalling ameliorates experimental colitis (Dinarello et al., 2013; Lopetuso et al., 2013).”