Role of Dialysis Modality in Responses of Blood Monocytes and Peritoneal Macrophages to Endotoxin Stimulation

Constitutive and endotoxin (lipopolysaccharide [LPS])-stimulated release of interieukin-1β (IL-1β), interieukin-6 (IL6), tumor necrosis factor-alpha (TNF-α), and prostaglandin E 2 (PGE 2 ) by blood monocytes and peritoneal cell preparations from patients on various forms of dialysis was measured. Monocytes were obtained from healthy controls (n = 20), and from patients on peritoneal dialysis (n = 8), on hemodialysis with cellulose ester membranes (n = 9), and on hemodialysis with polysulfone membranes (n = 8). Peritoneal macrophages were recovered by lavage during laparoscopic surgery from 11 healthy controls, from dialysate in 37 patients on peritoneal dialysis, and at catheter placement for transfer to peritoneal dialysis from eight patients on hemodialysis with polysulfone membranes. Peak LPS-induced production of TNF-α, IL-1β, and IL-6 by monocytes from patients on peritoneal dialysis and cellulose ester hemodialysis was less than that by monocytes from healthy controls. In contrast, monocytes from patients treated with polysulfone hemodialysis produced amounts of cytokine not different from controls. Lipopolysaccharide-stimulated PGE 2 production by monocytes was the same in both patient and control groups. Peritoneal cell preparations from patients on peritoneal dialysis showed decreased release of IL-1β and TNF-α as compared with control peritoneal cells and with their own blood monocytes. To determine whether the decreased response to LPS by peritoneal cells compared with their own blood monocytes could be attributed to lower numbers of macrophages in the peritoneal cell preparations, adherence of peritoneal cells to plastic was performed. Adherence increased the percentage of macrophages from 70% to more than 90%. In monocytes and adherence purified peritoneal macrophages from peritoneal dialysis patients, no significant difference between monocytes and adherent peritoneal macrophages could be found for TNF-α and PGE 2 . Interleukin-1β production by the adherent peritoneal macrophages, as by total peritoneal cells, was significantly lower than that by monocytes. Constitutive production of PGE 2 and IL-6 by peritoneal cells from patients on peritoneal dialysis was significantly increased. In contrast, LPS-stimulated production of TNF-α, IL-1β, and IL-6 by blood monocytes and peritoneal cells from patients receiving hemodialysis with polysulfone membranes was comparable to that produced by monocytes and peritoneal cells obtained from healthy controls. Thus, blood monocytes and peritoneal cells from patients on peritoneal dialysis and from patients on hemodialysis with cellulose-ester membranes demonstrate a decreased cytokine response to LPS, suggesting a state similar to endotoxin tolerance. In contrast, blood monocytes and peritoneal cells from patients on hemodialysis with a more "biocompatible" membrane showed a normal response to LPS stimulation, suggesting less prior chronic activation and therefore less "tolerance". Circulating IL-6 levels were increased in all patients on dialysis, but were highest in the plasma of patients on peritoneal dialysis. No increase in circulating levels of TNF-α was found in patients on peritoneal dialysis or in patients on hemodialysis prior to a mid-week dialysis treatment.