Impaired endotoxin-induced interleukin-1 beta secretion, not total production, of mononuclear cells from ESRD patients.

Abstract

Lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) production and secretion from peripheral blood mononuclear cells (PBMC) were determined in a longitudinal study with repeated measurements in PBMC from patients with chronic uremia not on hemodialysis (N = 8), end-stage renal disease (ESRD) patients (N = 8), and healthy controls (N = 7). ESRD patients were studied while using low-flux Cuprophan dialyzers and again using high-flux AN 69 dialyzers. Total (cell-associated plus secreted) LPS-induced IL-1 beta production was enhanced in uremic patients, but similar to controls in ESRD patients on Cuprophan. In contrast, LPS-induced IL-1 beta secretion (secreted amounts in % of total production) was similar to controls in uremic patients, but significantly reduced in ESRD patients on Cuprophan (P < 0.01). During AN 69 hemodialysis, LPS-induced total IL-1 beta production remained unchanged but IL-1 beta secretion increased significantly (P < 0.05) compared to Cuprophan dialysis. Increased IL-1 beta secretion coincided with a suppression in PGE2 synthesis (P < 0.02). Similarly, blockade of endogenous PGE2 by indomethacin increased LPS-induced IL-1 beta secretion (P < 0.01) but did not enhance total IL-1 beta production in PBMC from controls and patients on Cuprophan hemodialysis. Neither total production nor secretion of TNF alpha was different comparing the three study groups. We conclude that LPS-induced IL-1 beta secretion, but not total production, is impaired in PBMC from ESRD patients on long-term Cuprophan hemodialysis. This functional change in the PBMC response is specific for IL-1 beta, not due to uremia per se but hemodialysis-dependent and reversible. Hemodialysis with AN 69 suppresses endogenous PGE2 synthesis in PBMC which is associated with increased LPS-induced IL-1 beta secretion in the presence of unchanged total IL-1 beta production. We speculate that PGE2 could inactivate the IL-1 beta converting enzyme which is essential for processing and secretion of mature IL-1 beta.

• Authors: G Lonnemann, I Barndt, V Kaever, M Haubitz, R Schindler, S Shaldon, K M Koch
• Journal: Kidney international (Kidney Int) Vol. 47 Issue 4 Pg. 1158-67 (Apr 1995) ISSN: 0085-2538 [Print] United States
• PMID: 7783414 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Dinoprostone
• Indomethacin

Topics

• Adult
• Aged
• Analysis of Variance
• Dinoprostone (biosynthesis)
• Female
• Humans
• Indomethacin (pharmacology)
• Interleukin-1 (biosynthesis, blood)
• Kidney Failure, Chronic (blood, etiology, pathology, therapy)
• Leukocytes, Mononuclear (drug effects, metabolism, pathology)
• Lipopolysaccharides (pharmacology)
• Longitudinal Studies
• Male
• Middle Aged
• Radioimmunoassay
• Renal Dialysis
• Tumor Necrosis Factor-alpha (biosynthesis, drug effects)
• Uremia (blood, complications, pathology)