Induction of interleukin-1 and interleukin-1 receptor antagonist during contaminated in-vitro dialysis with whole blood

BACKGROUND: Previous studies on the permeability of cellulosic and syntheticdialysers for bacterial-derived cytokine-inducing substancesgave conflicting results. We tried to study this issue as closeto the in-vivo situation as possible. METHODS: An in-vitro dialysis circuit with whole human blood presentin the blood compartment of cuprophane (Cup), polysulphone (PS),and polyamide (PA) dialysers was employed; sterile filtratesderived from Pseudomonas aeruginosa cultures were added to thedialysate. We studied the induction of interleukin-1ß(IL-1ß) by plasma samples taken from the blood compartmentas well as the induction of IL-1ß and interleukin-1receptor antagonist (IL-1Ra) in mononuclear cells separatedfrom whole blood after circulation by radioimmunoassay and polymerasechain reaction. RESULTS: Plasma samples from the blood side of all dialysers inducedIL-1ß from non-circulated mononuclear cells afteraddition of pseudomonas filtrates to the dialysate; the maximalamount of IL-1ß induced by samples from the bloodcompartment was 4.8±1.2 ng/ml for Cup, 1.9±0.5ng/ml for PS, and 2.0±0.6 ng/ml for PA. Mononuclear cellsseparated after contaminated dialysis with all types of dialysersexpressed increased mRNA levels for IL-1ß and IL-1Ra.Production of IL-1Ra by cells separated after contaminated dialysiswas determined after Cup and PS dialysis; there was increasedproduction of IL-1Ra by these cells (Cup, 10.3±4.2; PS,7.3±2.5 ng/ml) compared to cells separated after steriledialysis (Cup, 5.6±2.1, P<0.05; PS, 4.5±1.1ng/ml, n.s.) or from non-circulated blood (Cup experiments,4.7±1.5, P<0.05; PS experiments, 4.1±1.2 ng/ml,n.s.). CONCLUSIONS: These data suggest penetration of cytokine-inducing substancesthrough both cellulosic and synthetic dialysers. Differencesbetween dialysers may exist regarding extent and time courseof penetration. The detection of cytokine mRNA as well as themeasurement of IL-1Ra synthesis is more sensitive substancesthrough dialyser membranes than the measurement of IL-1ßprotein synthesis.