Interleukin 18 and interleukin 18 binding protein: possible role in immunosuppression of chronic renal failure.
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.[1]References
- Interleukin 18 and interleukin 18 binding protein: possible role in immunosuppression of chronic renal failure. Dinarello, C.A., Novick, D., Rubinstein, M., Lonnemann, G. Blood Purif. (2003) [Pubmed]
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