Interleukin-18 in Inflammatory Kidney Disease

Abstract

Interleukin (IL)-18, a member of the IL-1 superfamily, is a pro-inflammatory cytokine that is structurally similar to IL-1β. IL-18 promotes the production of interferon gamma (IFN-γ) and strongly induces a Th1 response. IL-18 drives the same myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway as IL-1β. In physiological conditions, IL-18 is regulated by the endogenous inhibitor IL-18 binding protein (IL-18BP), and the activity of IL-18 is balanced. It is reported that in several inflammatory diseases, the IL-18 activity is unbalanced, and IL-18 neutralization by IL-18BP is insufficient. IL-18 acts synergistically with IL-12 to induce the production of IFN-γ as a Th1 cytokine, and IL-18 acts alone to induce the production of Th2 cytokines such as IL-4 and IL-13. In addition, IL-18 alone enhances natural killer (NK) cell activity and FAS ligand expression. The biological and pathological roles of IL-18 have been studied in many diseases. Here we review the knowledge regarding IL-18 signaling and the role of IL-18 in inflammatory kidney diseases. Findings on renal injury in coronavirus disease 2019 (COVID-19) and its association with IL-18 will also be presented.

The Mutual Contribution of 3-NT, IL-18, Albumin, and Phosphate Foreshadows Death of Hemodialyzed Patients in a 2-Year Follow-Up

“…The inflammasome—an intracellular platform created in response to pathogen-associated molecular patterns (PAMP) and danger-related molecular patterns (DAMP)—by converting procaspase-1 into active caspase-1, activates pro-inflammatory cytokines such as interleukin 1- (IL-1 ) and IL-18, thus triggering cell pyroptosis [ 19 , 20 ]. Recent studies have focused on the nucleotide-binding domain, leucine-rich repeats, pyrine-containing domain 3 (NLRP3) inflammasome role, which is widely activated in sterile inflammation [ 20 , 21 ]. NLRP3 is a sensor of cellular stress induced by both various external (pathogens) and internal factors (metabolic imbalance, organelle damage, and mitochondrial oxidative stress).…”

“…In our proposed predictive CV-mortality model, the inflammatory process was represented by IL-18, a cytokine that can regulate inflammation at multiple checkpoints [ 20 ]. Multifunctionality and participation in inflammatory cascades as well as innate and acquired immunity makes IL-18 an essential immune actor.…”

Avaliação e comparação de pacientes diabéticos e não diabéticos infectados pelo COVID-19 e fenótipos de gravidade: um estudo analítico e transversal em hospital de referência do Distrito Federal, Brasil

“…Interleukin-6, Tumor Necrosis Factor Alpha and Beta (TNF-α), adipocins are examples of inflammatory markers widely studied in metabolic syndrome, in which DM is inserted (Tanaka, 2016). However, with the advance of molecular medicine several other inflammatory substances have been discovered, some of which are even associated with specific complications of diabetes, and interleukin 18 can be cited, currently considered as amarker and prognostic factor in diabetes kidney disease (Satış et al, 2021;Hirooka & Nozaki, 2021). It should be noted here that this metainflammation or inflammatory storm as it is being termed does not lead to worse outcomes only in COVID-19, obviously.…”

Acute Kidney Injury: Biomarker-Guided Diagnosis and Management

“…The urinary markers tissue metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), which are recently discovered inducers of G1 cell-cycle arrest and are key stress biomarkers of AKI, are considered superior to known damage biomarkers such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) [ 21 ]. Interleukin (IL)-18, a pro-inflammatory cytokine that induces the production of interferon gamma, is detected in urine after acute proximal tubular damage [ 10 , 22 ]. Urine KIM-1, a transmembrane glycoprotein, is a proven marker of AKI in adults [ 23 ].…”