title: Interleukin 18 and interleukin 18 binding protein: possible role in immunosuppression of chronic renal failure.
abstract: Although interleukin (IL)-18 is a member of the IL-1 family of ligands, IL-18 appears to have unique characteristics, particularly in the regulation of the T helper type 1 (Th1) response. Th1 responses are required for tumor surveillance, killing intracellular organisms, and to provide help for antibody production. In patients with chronic renal failure, the well-known immunosuppression contributes to a failure to respond to infectious challenges and vaccinations. The most salient biological property of IL-18, linking this cytokine to the Th1 response, is its ability to induce interferon gamma (IFN-gamma). In fact, IL-18 was originally identified as an IFN-gamma-inducing factor, and IFN-gamma production is the hallmark of the Th1 response. Dysregulation of IFN-gamma production resulting from reduced activity of IL-18 would explain one of the mechanisms of immunosuppression in patients with chronic renal failure. The activity of IL-18 can be regulated by the IL-18-binding protein (IL-18BP), a glycoprotein of 40,000 daltons, which is constitutively expressed and appears to be the natural inhibitor of IL-18 activity. Unlike soluble receptors for IL-18, IL-18BP does not have a transmembrane domain; IL-18BP is a secreted protein possessing a high-affinity binding and ability to neutralize IL-18. IL-18BP was discovered in human urine and is excreted in health following glomerular filtration. With decreasing renal function, the concentrations of IL-18BP in the circulation are elevated as compared with subjects with a normal renal function, and these elevated levels may result in a decreased IL-18 activity. Because of the importance of IL-18 and IFN-gamma in the Th1 response, the biology of IL-18 and IL-18BP is reviewed here in the context of the immunosuppression of chronic renal failure.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colo 80262, USA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Daniela
authors.initials: D
authors.lastname: Novick
authors.forename: Menachem
authors.initials: M
authors.lastname: Rubinstein
authors.forename: Gerhard
authors.initials: G
authors.lastname: Lonnemann
mesh_terms: D000818:Animals; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000502:physiology; D020382:Interleukin-18 / Q000096:biosynthesis / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D007676:Kidney Failure, Chronic / Q000276:immunology*; D018123:Receptors, Interleukin / Q000378:metabolism; D053724:Receptors, Interleukin-18
chemical_list: D006023:Glycoproteins; C508572:IL18R1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; C118370:interleukin-18 binding protein; D018664:Interleukin-12; D007371:Interferon-gamma