The effect of peritoneal dialysis fluid on the release of IL-1 beta and TNF alpha by macrophages/monocytes.
OBJECTIVE
To study the effect of dialysis fluid on the release of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) by peritoneal macrophages (PM) and peripheral blood mononuclear cells (MNC), and the time course and factors involved in this effect.


METHODS
PM and MNC were incubated for various periods with Dianeal itself, or Dianeal of varying pH and composition. IL-1 beta was measured by radioimmunoassay and TNF alpha by cytotoxicity assay.


METHODS
PM were obtained by centrifugation of dialysis effluent from 3 continuous ambulatory peritoneal dialysis (CAPD) patients. MNC were obtained from healthy volunteers.


RESULTS
Dialysis fluid inhibited the release of both cytokines. Indomethacin had no effect on the inhibition of TNF alpha release caused by dialysis fluid. Thus prostaglandins are not involved in this inhibition. Solutions of pH 5.2 and high lactate concentration caused an identical inhibition to that caused by dialysate, whereas the presence or absence of glucose had no effect. Thus it seems that pH and lactate are the important inhibitory factors. Time course studies showed that the inhibition of TNF alpha release was substantial after only 15 minutes of incubation with dialysate, whereas the inhibition of IL-1 beta became significant only after 60 minutes of incubation.


CONCLUSIONS
Even though dialysate pH rises within 15-30 minutes after instillation into the abdomen, the initial low pH present for only a short time could have a significant effect on TNF alpha release by peritoneal macrophages, and thus on their ability to mount a normal inflammatory response. Lactate also has a significant inhibitory role. It is suggested that commercial dialysis solutions should have a pH of 7.0 and that a physiological buffer other than lactate be used.
Department of Nephrology, Soroka Medical Center, Beersheva, Israel.
A
A
Douvdevani
J
J
Rapoport
A
A
Konforti
M
M
Zlotnik
C
C
Chaimovitz
D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000378:metabolism*; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015314:Dialysis Solutions; D007375:Interleukin-1; D007773:Lactates; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D005947:Glucose