Generation of TNFalpha and interleukin-6 by peritoneal macrophages after overnight dwells with bicarbonate- or lactate-buffered dialysis fluid

Perit Dial Int. 2002 Nov-Dec;22(6):663-9.

Abstract

Objective: In order to evaluate the biocompatibility profile of a newly designed peritoneal dialysis fluid (PDF), we evaluated peritoneal leukocyte (PMphi) cytokine release following overnight in vivo dwells using standard, lactate-buffered, single-chamber bag PDF (Lac-PDF) and purely bicarbonate-buffered, double-chamber bag PDF containing 34 (Bic-PDF) or 39 (Bic Hi-PDF) mmol/L bicarbonate.

Design: A randomized, open, crossover clinical trial with single weekly test dwells was performed in stable, long-term continuous ambulatory PD patients (n = 8). During 8-hour overnight dwells, PMphi were exposed to different PDF containing 1.5% glucose. After drainage, peritoneal cells were isolated and incubated with RPMI 1640 medium for 2 or 3 hours, with and without stimulation by lipopolysaccharide (LPS). Ex vivo release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 was measured by specific ELISA technique.

Results: After pre-exposure to Lac-PDF, PMphi generated 242 +/- 279 pg TNFalpha/10(6) cells and 157 +/- 105 pg IL-6/10(6) cells. When pre-exposed to Bic-PDF and Bic Hi-PDF, TNFa and IL-6 production of PMphi was not significantly different from Lac-PDF. After LPS stimulation (100 ng/mL), PMD secretion of TNFalpha and IL-6 pre-exposed to three PDF revealed no significant differences between groups: TNFalpha was 2,864 +/- 1,216, 2,910 +/- 1,202, and 3,291 +/- 558 pg/10(6) cells after overnight dwells with Lac-PDF, Bic-PDF, and Bic Hi-PDF, respectively. Comparably, LPS-stimulated (100 pg/ mL) PMphi showed IL-6 secretion of 891 +/- 335, 1,380 +/- 1,149, and 1,442 +/- 966 pg/10(6) cells for Lac-PDF, Bic-PDF, and Bic Hi-PDF.

Conclusion: After long-term overnight dwells, initial pH, the different buffers, and varying glucose degradation product levels of PDF do not strongly affect PMphi function with respect to cytokine release. The lack of significant differences between fluids may result from the complete dialysate equilibration achieved during the overnight intraperitoneal dwell.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / analysis*
  • Bicarbonates / pharmacology*
  • Buffers
  • Cross-Over Studies
  • Dialysis Solutions / pharmacology*
  • Female
  • Humans
  • In Vitro Techniques
  • Interleukin-6 / analysis*
  • Interleukin-6 / metabolism*
  • Kidney Failure, Chronic / therapy*
  • Lactic Acid / pharmacology*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism*
  • Male
  • Middle Aged
  • Peritoneal Dialysis, Continuous Ambulatory*
  • Time Factors
  • Tumor Necrosis Factor-alpha / analysis*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Antineoplastic Agents
  • Bicarbonates
  • Buffers
  • Dialysis Solutions
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Lactic Acid