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 synthetic dialysers for bacterial-derived cytokine-inducing substances gave conflicting results. We tried to study this issue as close to the in-vivo situation as possible. Methods. An in-vitro dialysis circuit with whole human blood present in the blood compartment of cuprophane (Cup), polysulphone (PS), and polyamide (PA) dialysers was employed ; sterile filtrates derived from Pseudomonas aeruginosa cultures were added to the dialysate. We studied the induction of interleukin-1β (IL-1β) by plasma samples taken from the blood compartment as well as the induction of IL-1β and interleukin-1 receptor antagonist (IL-1Ra) in mononuclear cells separated from whole blood after circulation by radioimmunoassay and polymerase chain reaction. Results. Plasma samples from the blood side of all dialysers induced IL-1β from non-circulated mononuclear cells after addition of pseudomonas filtrates to the dialysate ; the maximal amount of IL-1β induced by samples from 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-1β and IL-1Ra. Production of IL-1Ra by cells separated after contaminated dialysis was determined after Cup and PS dialysis ; 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 sterile dialysis (Cup, 5.6 ± 2.1, P<0.05 ; PS, 4.5 ± 1.1 ng/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 substances through both cellulosic and synthetic dialysers. Differences between dialysers may exist regarding extent 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 membranes than the measurement of IL-1β protein synthesis.