Permeability of dialyzer membranes to TNFα-inducing substances derived from water bacteria

Abstract

Pro-inflammatory cytokine-inducing substances derived from cultured E. coli have previously been shown to pass across low-flux regenerated cellulosic dialyzer membranes. In the present study, a sterile filtrate of Pseudomonas maltophilia grown from standard bicarbonate dialysis fluid was used to test the permeability of various dialyzer membranes (regenerated cellulose, cellulose triacetate, polyacrylonitrile, polysulfone and polyamide) to TNF alpha-inducing bacterial substances. Pyrogen-free tissue culture medium (MEM) was recirculated for 60 minutes in the dialysate compartment of a closed-loop dialysis system, then P. maltophilia filtrate was added and recirculation was continued for a further hour. Samples from the dialysate (MEM) and the blood side (containing 10% human plasma in MEM) were incubated with donor mononuclear cells (MNC) for 18 hours and TNF alpha release was measured in MNC supernatants by radioimmunoassay. Five minutes after the addition of P. maltophilia filtrate, mean TNF alpha-inducing activity in the dialysate increased from (mean +/- SEM) 0.10 +/- 0.02 to 18.2 +2- 1.5 (ng/2.5 x 10(6) MNC/18 hr). TNF alpha-inducing activity in the blood side increased with regenerated cellulose from 0.10 +/- 0.01 to 4.57 +/- 1.55 (N = 8; P less than 0.001); with cellulose triacetate from 0.20 +/- 0.05 to 0.44 +/- 0.10 (N = 5; P less than 0.05), and with polyacrylonitrile from 0.10 +/- 0.02 to 1.16 +/- 0.45 (N = 5; P less than 0.03). No increased TNF alpha-inducing activity was observed in the blood side of polysulfone (N = 5) or polyamide dialyzers (N = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodialysis activates phospholipase A2 enzyme

“…In vitro studies clearly demonstrate that first, cytokine releasing agents cross the membranes from the dialysate to the blood side, second, complement factors induced during blood contact with dialysis membranes in vitro enhance transcription of IL-1 and third, cellulose directly stimulates cytokine production [9,36,37]. Thus in-vitro data clearly support the hypothesis of IL-1 to account for PLA 2 activation.…”

Reduced production of nitric oxide during haemodialysis

“…9,17,18 Yokokawa and colleagues have shown that NO production, detected as plasma levels of nitrite and nitrate, was increased in patients who had a hypotensive episode during haemodialysis (decrease in mean blood pressure Ͼ20 mm Hg) and was not increased in those who did not have a hypotensive episode. 19 Their results indicate that the increased production of NO is involved in the lowering of blood pressure during haemodialysis, and that the plasma levels of nitrite and nitrate are reliable markers for the in vivo production of NO.…”

Development, validation and applications of the monocyte activation test for pyrogens based on human whole blood

“…that this might indeed be crucial for judging the pyrogenic load for a dialysis patient was assessed by Marion-Ferey et al, who tested scrapings of bacterial biofilms in dialysis tubes and found a 20-fold higher response in the WBt than in the lAl (Marion-Ferey et al, 2005). the passage of cytokine-inducing substances, not only endotoxins, but exotoxins and peptidoglycans as well, through the dialysis membrane has been demonstrated (evans and Holmes, 1991;lonnemann et al, 1992;Urena et al, 1992;tsuchida et al, 1997).…”