The Interleukin-1 Family: Back to the Future

Abstract

Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. The IL-1 family includes 7 ligands with agonist activity (IL-1α and β, IL-18, IL-33, IL-36α, β, γ), three receptor antagonists (IL-1Ra, IL-36Ra, IL-38) and an anti-inflammatory cytokine (IL-37). Members of the IL-1 Receptor (IL-1R) family include 6 receptor chains forming 4 signaling receptor complexes, two decoy receptors (IL-1R2, IL-18BP) and two negative regulators (TIR8 or SIGIRR, IL-1RAcPb). A tight regulation via receptor antagonists, decoy receptors and signaling inhibitors ensures a balance between amplification of innate immunity and uncontrolled inflammation. All cells of the innate immune system express and/or are affected by IL-1 family members. Moreover, IL-1 family members play a key role in the differentiation and function of polarized innate and adaptive lymphoid cells. Here we will review the key properties of IL-1 family members, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.

The immune network in thyroid cancer

“…and cytokines (IL-6, TNF-a, and TGF-b). 8 IL-1 stimulated thyroid cell proliferation and the in vitro production of IL-8. 9 In a study performed on 115 patients affected by a variety of thyroid conditions and 30 controls, IL-1b serum concentrations allowed discrimination between individuals with atrophic thyroiditis and those with PTC, which displayed the highest and the lowest values, respectively.…”

Ten‐year alcohol consumption typologies and trajectories of C‐reactive protein, interleukin‐6 and interleukin‐1 receptor antagonist over the following 12 years: a prospective cohort study

“…The IL‐1 receptor antagonist (IL‐1 RA) is an endogenous inhibitor of IL‐1 that prevents the activation of the IL‐1 receptor by either IL‐1α or IL‐1β 21. IL‐1 RA is associated with a diverse range of diseases including CVD, type 2 diabetes, certain cancers and joint diseases such as arthritis 21, 22, 23, 24, 25. In a recent large‐scale Mendelian randomization study, it was found that genetically elevated levels of IL‐1 RA were causally associated with an increased risk of CHD and abdominal aortic aneurysm 26.…”

Characterization of SIGIRR/IL-1R8 Homolog from Zebrafish Provides New Insights into Its Inhibitory Role in Hepatic Inflammation

“…However, limited evidence shows the functions of SIGIRR in the liver. Previous tissue expression analyses showed that SIGIRR widely distributes in various tissues examined (2,50). However, the expression levels in tissues differ among various species.…”

“…Toll/IL-1R (TIR)8 or IL-1R8, is an important member of the TLR/IL-1R superfamily (1)(2)(3)(4). In contrast with other TIR family members, SIGIRR comprises a single extracellular Ig domain, a transmembrane region, and a conserved intracellular TIR domain with substitutions of the two amino acid sites (Ser 447 and Arg-Tyr 536 ) required for the signaling of IL-1RI, as well as a unique 95-aa-long cytoplasmic tail, which differentiates SIGIRR from other TIR-containing family members (4,5).…”