Proceedings of the 20th ISBP Meeting

Interleukin 18 and Interleukin 18 Binding Protein: Possible Role in Immunosuppression of Chronic Renal Failure
Charles A. Dinarello^a, Daniela Novick^b, Menachem Rubinstein^b, Gerhard Lonnemann<sup>c

a</sup>University of Colorado Health Sciences Center, Denver, Colo., USA;
^bWeizmann Institute of Science, Rehovot, Israel;
^cMedizinische Hochschule, Hannover, Germany

Address of Corresponding Author

Blood Purif 2003;21:258-270 (DOI: 10.1159/000070699)

  Key Words

• Chronic renal failure, immunosuppression
• Interleukin 18
• Interleukin 18 binding protein

  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-). In fact, IL-18 was originally identified as an IFN--inducing factor, and IFN- production is the hallmark of the Th1 response. Dysregulation of IFN- 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- 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.

Copyright © 2003 S. Karger AG, Basel

  Author Contacts

Charles A. Dinarello, MD
Department of Medicine, B168
University of Colorado Health Sciences Center, 4200 East 9th Ave.
Denver, CO 80262 (USA)
Tel. +1 303 315 3589, Fax +1 303 315 8054

  Article Information

Number of Print Pages : 13
Number of Figures : 3, Number of Tables : 1, Number of References : 81