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 syn thetic dialysers for bacterial-derived cytokine-inducing substances gr ave conflicting results. We tried to study this issue as close to the in-vivo situation as possible. Methods. An in-vitro dialysis circuit w ith whole human blood present in the blood compartment of cuprophane ( Cup), polysulphone (PS), and polyamide (PA) dialysers was employed; st erile filtrates derived from Pseudomonas aeruginosa cultures were adde d to the dialysate. We studied the induction of interleukin-1 beta (IL -1 beta) by plasma samples taken from the blood compartment as well as the induction of IL-1 beta and interleukin-1 receptor antagonist (IL- 1Ra) in mononuclear cells separated from whole blood after circulation by radioimmunoassay and polymerase chain reaction. Results. Plasma sa mples from the blood side of all dialysers induced IL-1 beta from non- circulated mononuclear cells after addition of pseudomonas filtrates t o the dialysate; the maximal amount of IL-1 beta induced by samples fr om the blood compartment was 4.8+/-1.2 ng/ml for Cup, 1.9+/-0.5 ng/ml for PS, and 2.0+/-0.6 ng/ml for PA. Mononuclear cells separated after contaminated dialysis with all types of dialysers expressed increased mRNA levels for IL-1 beta and IL-1Ra. Production of IL-1Ra by cells se parated after contaminated dialysis was determined after Cup and PS di alysis; there was increased production of IL-1Ra by these cells (Cup, 10.3+/-4.2; PS, 7.3+/-2.5 ng/ml) compared to cells separated after ste rile dialysis (Cup, 5.6+/-2.1, P<0.05; PS, 4.5+/-1.1 ng/ml, n.s.) or f rom non-circulated blood (Cup experiments, 4.7+/-1.5, P<0.05; PS exper iments, 4.1+/-1.2 ng/ml, n.s.). Conclusions. These data suggest penetr ation of cytokine-inducing substances through both cellulosic and synt hetic dialysers. Differences between dialysers may exist regarding ext ent and time course of penetration. The detection of cytokine mRNA as well as the measurement of IL-1Ra synthesis is a more sensitive marker for the transfer of cytokine-inducing substances through dialyser mem branes than the measurement of IL-1 beta protein synthesis.