The effect of peritoneal dialysis fluid on the release of IL-1β and TNFα by macrophages/monocytes

Objective: To study the effect of dialysis fluid on the release of interleukin-1β (IL-1β) and tumor necrosis factor (TNFα) by peritoneal macrophages (PM) and peripheral blood mononuclear cells (MNC), and the time course and factors involved in this effect. Design: PM and MNC were incubated for various periods with Dianeal itself, or Dianeal of varying pH and composition. IL-1β was measured by radioimmunoassay and TNFα by cytotoxicity assay. Patients: 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 TNFα 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 TNFα release was substantial after only 15 minutes of incubation with dialysate, whereas the inhibition of IL-1β 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 TNFα 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.