Increased Production of lnterleukin-1β and lnterleukin-1 Receptor Antagonist by Peripheral Blood Mononuclear Cells in Undialyzed Chronic Renal Failure

Abstract

We investigated the cell content and production of IL-1β and IL-1 receptor antagonist (Ra) by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) obtained from 15 undialyzed patients with chronic renal failure (CRF; estimated GFR < 10ml/min), 15 patients on chronic hemodialysis (HD) and 15 healthy controls. These cytokines were measured by ELISA. The cell content of IL-1β in freshly obtained PBMC was not detectable in any group. In contrast, that of IL-1Ra in CRF (1,807 ± 370 pg/ml, p < 0.05) as well as in HD( 1,791 ± 151 pg/mlp < 0.001) was significantly higher than that of the controls (907 ± 156 pg/ml). In unstimulated cultured PBMC, spontaneous production of IL-1β in CRF (66 ± 13 pg/ml, p < 0.05) and in HD (81 ± 29 pg/ml, p < 0.05) was significantly higher than that of the controls (26 ± 3 pg/ml). In contrast, comparison of spontaneous production of IL-1Ra in the three groups was not significantly different. In LPS-stimulated PBMC, IL-1β production in CRF (10,896 ± 1,359 pg/ml, p < 0.01) and in HD(11,441 ± 1,400 pg/ml, p < 0.01) was significantly higher than that of the controls (6,117 ± 572 pg/ml). However, IL-1Ra production by LPS-stimulated PBMC in the three groups was not significantly different. Moreover, the spontaneous IL-lRa/IL-1β production ratio in CRF (140 ± 16, p < 0.01) and in HD (142 ± 19, p < 0.01) was significantly lower than that of the controls (294 ± 41). The present study demonstrates that cytokine production by PBMC in undialyzed CRF patients as well as in hemodialyzed patients is heightened and may induce impaired function of the immunological system before CRF patients are introduced to dialysis.