THE EFFECTS OF ENDOTOXIN-CONTAMINATED DIALYSATE AND POLYSULFONE OR CELLULOSIC MEMBRANES ON THE RELEASE OF TNF-ALPHA DURING SIMULATED DIALYSIS

Simulated dialysis of whole blood was used to determine whether membra ne factors (biocompatibility), endotoxin (ET) membrane diffusion, or t ransmembrane monocyte-ET interactions would stimulate tumor necrosis f actor (TNF alpha) release. Whole blood containing EDTA and aprotinin w as recirculated in the blood compartment of hollow fiber dialyzers con taining either regenerated cellulose or polysulfone membranes. ET-free and ET-spiked dialysate were recirculated consecutively in the dialys ate compartment for 30 min each. Blood and dialy-sate samples were col lected at t(0) and after each 30 min of simulated dialysis for determi nation of TNF alpha and ET concentrations. TNF alpha was not detected in any blood samples collected after simulated dialysis with regenerat ed cellulose (RC) membranes and ET-free or ET-spiked dialysate. Howeve r, blood ET concentrations, as determined by the Limulus amebocyte lys ate (LAL) assay, increased in RC dialyzers after each 30 min of simula ted dialysis even with ET-free dialysate. Since TNF alpha was not dete cted in these blood samples; the material detected by the LAL assay pr obably was not ET but an LAL-reactive material. After simulated dialys is with polysulfone dialyzers and ET-free dialysate, TNF alpha and ET were not detected in blood samples. ET also was not detected in blood samples after dialysis with ET-spiked dialysate. However, TNF alpha wa s detected in 7 of 13 (54%) of the blood samples following the 500 ng/ ml of ET dialysate spike. TNF alpha release during simulated dialysis with polysulfone membranes and ET-contaminated dialysate may be due to transmembrane stimulation of circulating mononuclear cells and not di ffusion of ET across the membrane.