Details

Autor(en) / Beteiligte

• Perianayagam, Mary C.
• Jaber, Bertrand L.
• Guo, Daqing
• King, Andrew J.
• Pereira, Brian J.G.
• Balakrishnan, Vaidyanathapuram S.

Titel

Defective Interleukin-10 Synthesis by Peripheral Blood Mononuclear Cells among Hemodialysis Patients

Ist Teil von

• Blood purification, 2002-01, Vol.20 (6), p.543-550

Ort / Verlag

Basel, Switzerland: Karger

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• 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-α 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-α by PBMC did not differ between the 2 groups. In the HD patients, there was an inverse correlation between TNF-α and IL-10 synthesis by ET-stimulated PBMC, suggesting a regulatory effect of IL-10 on PBMC TNF-α synthesis. There was also an inverse correlation between plasma albumin and ET-stimulated TNF-α synthesis by PBMC among HD patients. TNF-α 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.