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Leukotriene B4 and tumor necrosis factor release from leukocytes: effect of peritoneal dialysate
Abstract:
The effect of peritoneal dialysate on the capacity of peripheral blood polymorphonuclear (PMNL) and mononuclear leukocytes (MNC) to release leukotriene B4 (LTB4) and tumor necrosis factor alpha (TNF alpha) was investigated in vitro. Following density gradient separation, aliquots of 5 x 10(6) PMNL or MNC were incubated in peritoneal dialysis fluid containing 1.5% glucose or Hanks' buffer (= control) for 1-2 h at 37 degrees C. TNF alpha and LTB4 production was stimulated with Escherichia coli lipopolysaccharide (LPS) and calcium ionophore A23187, respectively. MNC incubated in buffer and LPS produced (mean +/- SD) 1,006 +/- 522 pg TNF alpha/5 x 10(6) cells; no significant amounts of TNF alpha were detectable in the presence of dialysate. An inhibition of TNF alpha release was also observed in MNC exposed to bicarbonate-buffered dialysates (pH 7.40) and 4.25% and 1.5% glucose solution with physiologic osmolality. Incubation of PMNL in Hanks' buffer followed by A23187 stimulation led to production of 29.1 +/- 19.2 ng LTB4/5 x 10(6) cells, whereas glucose-incubated cells were refractory to ionophore stimulation (less than 0.1 ng LTB4/5 x 10(6) cells). The failure of dialysate-exposed leukocytes to release inflammatory mediators in response to adequate stimuli may contribute to the impairment of cellular host defense in the setting of continuous ambulatory peritoneal dialysis.
Insights
Peritoneal dialysate significantly impairs the ability of leukocytes to release key inflammatory mediators like tumor necrosis factor alpha and leukotriene B4. This suggests a potential mechanism for weakened immune defense during peritoneal dialysis.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Continuous ambulatory peritoneal dialysis (CAPD) is a common renal replacement therapy.
- Leukocytes play a crucial role in host defense through the release of inflammatory mediators.
- The impact of peritoneal dialysate on leukocyte function requires further investigation.
Purpose of the Study:
- To investigate the in vitro effect of peritoneal dialysate on leukocyte inflammatory mediator release.
- To assess the capacity of peripheral blood polymorphonuclear (PMNL) and mononuclear leukocytes (MNC) to release leukotriene B4 (LTB4) and tumor necrosis factor alpha (TNF alpha) when exposed to dialysate.
Main Methods:
- PMNL and MNC were isolated using density gradient centrifugation.
- Cells were incubated in peritoneal dialysis fluid (1.5% glucose) or Hanks' buffer (control).
- TNF alpha and LTB4 production were stimulated with lipopolysaccharide (LPS) and calcium ionophore A23187, respectively.
Main Results:
- Peritoneal dialysate significantly inhibited TNF alpha release from MNC stimulated with LPS.
- PMNL incubated in dialysate were refractory to LTB4 release stimulation by calcium ionophore.
- Inhibition of mediator release was observed across various dialysate compositions, including bicarbonate-buffered and different glucose concentrations.
Conclusions:
- Peritoneal dialysate impairs the capacity of leukocytes to release critical inflammatory mediators.
- This functional impairment may contribute to the compromised cellular host defense observed in CAPD patients.
- Further research is warranted to explore strategies to mitigate these effects.