Interleukin-18, interleukin-18 binding protein and impaired production of interferon-gamma in chronic renal failure.

Abstract

UNLABELLED:

Uremia is associated with suppressed cellular immune responses, manifested, in part, by impaired interferon-gamma (IFNgamma) production. We investigated the influence of kidney function on plasma levels of interleukin-18 binding protein (IL-18BP), the naturally occurring inhibitor of IL-18.

METHODS:

Plasma levels of IL-18, IL-18BP and IFNgamma were measured by specific immunoassays in patients with normal kidney function (NKF, n = 29), in patients with chronic renal insufficiency (CRI, n = 29), and in patients on hemodialysis (HD, n = 40). In addition, Staphylococcus epidermidis-induced production of IFNgamma and IL-18 in whole blood cultures was determined in 12 patients on HD and compared to production in 9 controls with NKF.

RESULTS:

Plasma IL-18 (mean +/- SEM) in NKF was 17.9 +/- 3.6 pg/ml, in CR142.6 +/- 7.0 pg/ml (p < 0.01), and in HD 93.5 +/- 13.6 pg/ml (p < 0.001). The level of IL-18BP in NKF was 3.4 +/- 0.4 ng/ml, in CRI 7.5 +/- 0.7 ng/ml (p < 0.001), and in HD 13.1 +/- 0.8 ng/ml (p < 0.001). Plasma IL-18BP was inversely correlated with creatinine clearance (correlation coefficient: -0.7479). The level of free IL-18 was calculated in NKF to be 13.8 +/- 3.3 pg/ml, in CRI 23.6 +/- 3.9 pg/ml (not significant), and in HD 39.6 +/- 5.9 pg/ml (p < 0.001). Stimulated whole blood production of IFNgamma in NKF was 185 +/- 74 pg/10(6) mononuclear cells (PBMC), but suppressed in HD to 27.3 +/- 16 pg/10(6) PBMC (p < 0.05).

CONCLUSION:

In uremia, retention of IL-18BP does not suffice to neutralize most of the concomitantly raised levels of total IL-18 resulting in elevated levels of free IL-18. Nevertheless, IFNgamma production in whole blood is reduced in patients on HD. Therefore, suppression of IFNgamma production in uremia may be due to inhibitors of IFNgamma production other than IL-18BP.

• Authors: G Lonnemann, D Novick, M Rubinstein, C A Dinarello
• Journal: Clinical nephrology (Clin Nephrol) Vol. 60 Issue 5 Pg. 327-34 (Nov 2003) ISSN: 0301-0430 [Print] Germany
• PMID: 14640238 (Publication Type: Journal Article)

Chemical References

• Glycoproteins
• Intercellular Signaling Peptides and Proteins
• Interleukin-18
• interleukin-18 binding protein
• Interferon-gamma

Topics

• Adult
• Aged
• Female
• Glycoproteins (blood)
• Humans
• Intercellular Signaling Peptides and Proteins
• Interferon-gamma (biosynthesis)
• Interleukin-18 (blood)
• Kidney Failure, Chronic (metabolism)
• Male
• Middle Aged