Defective interleukin-10 synthesis by peripheral blood mononuclear cells among hemodialysis patients.
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.


CONCLUSIONS
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.
Perianayagam
Mary C
MC
Division of Nephrology, Department of Medicine, New England Medical Center Hospitals, 750 Washington Street, Boston, MA 02111, USA.
Jaber
Bertrand L
BL
Guo
Daqing
D
King
Andrew J
AJ
Pereira
Brian J G
BJ
Balakrishnan
Vaidyanathapuram S
VS
D000328:Adult; D000368:Aged; D001773:Blood Cells; D016022:Case-Control Studies; D025461:Feedback, Physiological; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D016753:Interleukin-10 / Q000096:biosynthesis*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10