title: Cytokine production during in vitro hemodialysis with new and formaldehyde- or renalin-reprocessed cellulose dialyzers.
abstract: Critics of reuse have suggested that patients treated with reprocessed dialyzers are exposed to pyrogen trapped from the water or solutions used during the reprocessing cycle, thereby triggering the synthesis and release of proinflammatory cytokines, resulting in cachexia. To test this hypothesis, the production of interleukin (IL)-1 alpha by peripheral blood mononuclear cells (PBMC) during in vitro dialysis with new or reprocessed cellulose dialyzers was compared. An in vitro closed-loop dialysis circuit was created with standard hemodialysis blood lines and either new cellulose dialyzers or dialyzers reprocessed 10 times with either formaldehyde/bleach (formaldehyde) or peracetic acid/hydrogen peroxide mixture (Renalin). The circuit was rinsed with 2 L or more of pyrogen-free normal saline before the start of in vitro dialysis until the blood compartment tested negative for residual formaldehyde/Renalin. Heparinized whole blood from healthy volunteers was circulated for 3 h in the blood compartment at 100 mL/min at 37 degrees C. The dialysate compartment was sealed. Peripheral blood mononuclear cells (PBMC) were harvested from the blood compartment before and at the end of 3 h of in vitro dialysis. Total IL-1 alpha synthesis (cell associated plus secreted) by unstimulated and endotoxin-stimulated PBMC was measured by a specific, non-cross-reactive radioimmunoassay. After 3 h of in vitro dialysis, IL-1 alpha production (in picograms per 2.5 million PBMC) by unstimulated PBMC increased from 354 +/- 63 at baseline to 454 +/- 57 with new dialyzers (P = 0.25), from 453 +/- 101 to 450 +/- 67 with formaldehyde-reprocessed dialyzers (P = 0.98), and from 360 +/- 61 to 538 +/- 144 with Renalin-reprocessed dialyzers (P = 0.23). IL-1 alpha production by endotoxin-stimulated PBMC increased from 5,214 +/- 996 to 9,237 +/- 929 with new dialyzers (P < = 0.001), from 6,395 +/- 955 to 9,636 +/- 1,058 with formaldehyde-reprocessed dialyzers (P = 0.006), and from 7,561 +/- 1,000 to 10,092 +/- 2,470 with Renalin-reprocessed dialyzers (P = 0.32). However, there were no significant differences among groups with respect to IL-1 alpha production by unstimulated or endotoxin-stimulated PBMC either before or after 3 h of in vitro dialysis. These data argue against the suggestion that exposure to reprocessed dialyzers results in enhanced synthesis of proinflammatory cytokines. In fact, reprocessed dialyzers probably induce less cytokine production than do new cellulose dialyzers.
authors.affiliation: Division of Nephrology, New England Medical Center, Boston, MA 02111, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Pereira
authors.forename: B
authors.initials: B
authors.lastname: Snodgrass
authors.forename: G
authors.initials: G
authors.lastname: Barber
authors.forename: C
authors.initials: C
authors.lastname: Perella
authors.forename: S
authors.initials: S
authors.lastname: Chopra
authors.forename: A J
authors.initials: AJ
authors.lastname: King
mesh_terms: D002482:Cellulose; D004731:Endotoxins / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D008567:Membranes, Artificial; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010463:Peracetic Acid / Q000494:pharmacology; D006435:Renal Dialysis / Q000295:instrumentation*
chemical_list: D004731:Endotoxins; D007375:Interleukin-1; D008567:Membranes, Artificial; D005557:Formaldehyde; D002482:Cellulose; D006861:Hydrogen Peroxide; D010463:Peracetic Acid