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Defective interleukin-10 synthesis by peripheral blood mononuclear cells among hemodialysis patients
Mary C Perianayagam1, Bertrand L Jaber, Daqing Guo
1Division of Nephrology, Department of Medicine, New England Medical Center Hospitals, 750 Washington Street, Boston, MA 02111, USA.
Background:
Interleukin-10 (IL-10), a potent regulatory monokine produced by activated mononuclear cells, provides an efficient autocrine mechanism for controlling proinflammatory cytokine synthesis. We hypothesized that defective synthesis of IL-10 could contribute to the inflammatory state in hemodialysis (HD) patients due to impaired feedback inhibition of proinflammatory cytokine production.
Methods:
We compared peripheral blood mononuclear cell (PBMC) synthesis and transcription of IL-10 and TNF-alpha in 12 patients with end-stage renal disease on long-term maintenance HD and a control group of 10 healthy subjects.
Results:
The synthesis of IL-10 by unstimulated PBMC was detectable in 5 of 12 (42%) HD patients as compared to 7 of 10 (70%) controls (p = 0.02). IL-10 synthesis in response to endotoxin (ET) by PBMC from HD patients was significantly lower when compared to the robust response in the control group (p = 0.008). Among the HD patients, there was a positive correlation between ET-stimulated IL-10 synthesis and the duration of time on dialysis. Unstimulated and ET-stimulated synthesis of TNF-alpha by PBMC did not differ between the 2 groups. In the HD patients, there was an inverse correlation between TNF-alpha and IL-10 synthesis by ET-stimulated PBMC, suggesting a regulatory effect of IL-10 on PBMC TNF-alpha synthesis. There was also an inverse correlation between plasma albumin and ET-stimulated TNF-alpha synthesis by PBMC among HD patients. TNF-alpha mRNA expression did not differ in HD patients relative to healthy controls. In contrast, when IL-10 mRNA from ET-stimulated PBMC was quantified, there was marked difference between the 2 groups indicating a transcriptional defect in IL-10 synthesis in PBMC from HD patients.
Conclusion:
Our observations indicate a marked abnormality in IL-10 synthesis by PBMC from HD patients probably related to a transcriptional defect. Low PBMC IL-10 synthesis may contribute to a chronic inflammatory state in these patients by defective feedback inhibition of proinflammatory cytokine production.
