Imbalanced production of IL-18 and its antagonist in human diseases, and its implications for HIV-1 infection. (June 2016)

• Record Type: Journal Article
• Authors: Samarani, Suzanne; Allam, Ossama; Sagala, Patrick; Aldabah, Zainab; Jenabian, Mohammad-Ali; Mehraj, Vikram; Tremblay, Cécile; Routy, Jean-Pierre; Amre, Devendra; Ahmad, Ali
• Is Part Of: Cytokine. Volume 82(2016)
• Page Start: 38
• Page End: 51
• Publication Date: 2016-06
• Subjects: AcPL accessory protein-like or IL-18 receptor β chain -- ACTH adrenocorticotrophic hormone -- ASC apoptosis-associated speck-like protein with CARD domain -- ANP atrial natriuretic peptide -- BIR baculovirus inhibitor of apoptosis protein repeat -- cART combination antiretroviral therapy -- CARD caspase activation and recruitment domain -- DAMPs danger-associated molecular patterns -- Egr-1 early growth response-1 -- GAS gamma interferon-activated sequences -- HAART highly active antiretroviral therapy -- HPA hypothalamus–pituitary–adrenal axis -- ICAM-1 intercellular adhesion molecule-1 or CD54 -- ICE IL-1 converting enzyme or caspase-1 -- IDO-1 indoleamine 2, 3-dioxygenase-1 -- IL-1RrP IL-1 receptor-related protein or IL-18 receptor α chain -- IRF-1 interferon regulatory factor-1 -- LRR leucine-rich repeat -- LTNP long-term non-progressors -- NACHT a domain present in NAIP (neuronal inhibitor of apoptosis)/CIITA (major histocompatibility complex class II transactivator)/HET-E (plant het product involved in vegetative incompatibility) and TP-1 (telomerase-associated protein 1) -- NIAPs neuronal inhibitor of apoptosis proteins -- NLR NOD-like receptor -- NLRC NLR with CARD domain -- NLRP NLR with pyrin domain -- NRTI nucleoside reverse transcriptase inhibitor -- OPN osteopontin -- P2RX7 purinergic receptor P2X and ligand-gated ion channel 7 -- PAMPs pathogen-associated molecular patterns -- PARP poly ADP-ribose polymerase -- PD-L 1 programmed death-ligand-1 -- PIs protease inhibitors -- PS phosphatidylserine -- PYD pyrin domain -- SHS secondary haemophagocytic syndrome -- SHIV recombinant human immunodeficiency virus (HIV-1) containing envelope proteins from simian immunodeficiency virus (SIV) -- TIR Toll/IL-1 receptor homology domain -- TRIM tripartite motif -- V-CAM-1 vascular cell adhesion molecule-1 or CD106; IL-18 -- IL-18BP -- IL-37 -- HIV-1 -- AIDS -- cART -- Inflammasome -- Caspase-1; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.01.006
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IL-18 is normally kept inactive by its antagonist, IL-18BP, in the circulation. It induces production of IL-18BP as a negative feedback response in healthy state. IL-18 levels are increased in the circulation of HIV-infected patients. The patients show compromised negative feedback response. Sustained higher levels of IL-18 despite cART predict treatment failure. Abstract: IL-18 is a pleiotropic and multifunctional cytokine that belongs to the IL-1 family. It is produced as a biologically inactive precursor, which is cleaved into its active mature form mainly by caspase-1. The caspase becomes active from its inactive precursor (procaspase-1) upon assembly of an inflammasome. Because of IL-18's potential pro-inflammatory and tissue destructive effects, its biological activities are tightly controlled in the body by its naturally occurring antagonist called IL-18BP. The antagonist is produced in the body both constitutively and in response to an increased production of IL-18 as a negative feedback mechanism. Under physiological conditions, most of IL-18 in the circulation is bound with IL-18BP and is inactive. However, an imbalance in the production of IL-18 and its antagonist (an increase in the production of IL-18 with a decrease, no increase or an insufficient increase in the production of IL-18BP) has been described in many chronic inflammatory diseases in humans. The imbalance results in an increase in the concentrations of free IL-18 (unbound with its antagonist) resulting in increased biological activities of the cytokine that contribute towards pathogenesis of the disease. In this article, we provide an overview of the current biology of IL-18 and its antagonist, discuss how the imbalance occurs in HIV infections and how it contributes towards development of AIDS and other non-AIDS-associated clinical conditions occurring in HIV-infected individuals undergoing combination anti-retroviral therapy (cART). Finally, we discuss challenges facing immunotherapeutic strategies aimed at restoring balance between IL-18 and its antagonist in these patients.