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Effect of CAPD dialysate on the release of eicosanoids and cytokines from human peritoneal macrophages
H B Steinhauer1, U Brugger, R Atmanspacher
1Dept. of Internal Medicine, University of Freiburg, F.R. Germany.
Abstract:
The effect of fresh peritoneal dialysis (PD) solution and effluent on the generation of eicosanoids and cytokines by human peritoneal macrophages (PMO) was studied in vitro. PMO, isolated by density gradient separation from patients undergoing intermittent peritoneal dialysis (IPD), were incubated for 2 h with PD effluent after dwell periods of 5 to 240 min or fresh PD solution. Supplemented RPMI-1640 medium served as control. PMO were stimulated by calcium ionophore A23187 (10 M). PD solution significantly inhibited the release of prostanoids (PGE2, TXB2, 6-k-PGF1), leukotrienes (LTB4, LTC4), and cytokines (11-6, TNF) from PMO by 60 to 96% (p < 0.05). Addition of A23187 increased the generation of TXB2, LTB4, and LTC4 in PD solution adjusted to pH 7.4 to 2.7 up to 28.6 times the basal level, but was ineffective in PD fluid at pH 5.2. Incubation of PMO with PD effluent of varying dwell times resulted in a rise of all assayed mediators (p < 0.05). The release of IL-6 increased continuously from 80 +/- 10 pg/10(6) PMO (0 min dwell time) to 440 +/- 104 pg/10(6) PMO (4 h dwell time, mean +/- S.E.M.). TNF generation rose from 6.0 +/- 0.1 pg/10(6) PMO (0 min dwell time) to 162 +/- 54 pg/10(6) PMO after 5 min dwell time and remained constant with effluents of longer dwell times (15 to 240 min). Exposure of PMO to PD effluents after 240 min dwell time tended to decrease the median levels of PGE2, TXB2, and 6-k-PGF1.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Peritoneal dialysis solution suppresses inflammatory mediator release from human peritoneal macrophages (PMO). However, PD effluent with longer dwell times increases mediator generation, suggesting a complex inflammatory response in PD patients.
Area of Science:
- Immunology
- Nephrology
- Biochemistry
Background:
- Peritoneal macrophages (PMO) play a crucial role in the peritoneal membrane's inflammatory response during peritoneal dialysis (PD).
- Understanding the impact of PD solutions and effluent on PMO function is vital for managing PD-related complications.
Purpose of the Study:
- To investigate the in vitro effects of fresh PD solution and PD effluent on the generation of eicosanoids and cytokines by human PMO.
- To assess how varying dwell times of PD effluent influence mediator release from PMO.
Main Methods:
- Human PMO were isolated from patients undergoing intermittent PD (IPD).
- PMO were incubated with fresh PD solution or PD effluent of varying dwell times (5-240 min).
- Cells were stimulated with calcium ionophore A23187, and mediator release (prostanoids, leukotrienes, cytokines) was quantified.
Main Results:
- Fresh PD solution significantly inhibited the release of prostanoids, leukotrienes, and cytokines from PMO (60-96% reduction).
- PD effluent with increasing dwell times led to a significant rise in all measured mediators, particularly IL-6 and TNF.
- The pH of PD solution influenced mediator generation, with higher generation at pH 7.4 compared to pH 5.2.
Conclusions:
- Fresh PD solution exhibits an anti-inflammatory effect on human PMO in vitro.
- Accumulated PD effluent, especially after longer dwell times, stimulates the release of inflammatory mediators from PMO.
- These findings highlight the dual role of PD components in modulating peritoneal inflammation and suggest potential targets for intervention.
