Activation of mononuclear cells by aqueous extracts from hollow-fibre haemodialysers

Monocytes from patients treated by long-term haemodialysis with cellulosic membranes can show functional signs of activation depending on the dialyser module. To elucidate the mechanism of this phenomenon, aqueous extracts of various hollow-fibre dialysers were tested for their ability to induce in-vitro interleukin-1 generation in peripheral blood mononuclear cells from healthy donors. Extracts were prepared by passing 0.5 litres of sterile endotoxin-free water from the dialysate to the blood compartment of the dialyser. Different dialysers containing cellulosic membranes, i.e. cuprophan, and hemophan, were studied. Extracts were dried by lyophilisation and resuspended in cell culture medium before incubation with peripheral blood mononuclear cells for 18 hours at 37 degrees C in a 5% CO2 atmosphere. Interleukin-1 was assayed by biological or radioimmunological methods. Extracts from steam-autoclaved, dry-stored, or gamma-sterilised, wet-stored cuprophan and hemophan modules resulted in interleukin-1 activity that did not differ from negative controls. By contrast, extracts from cuprophan caused significant interleukin-1 production when prepared from ethylene oxide-sterilised, dry-stored dialysers. This monokine-inducing activity could not be neutralised by the addition of polymyxin B and was heat unstable, indicating that the cell-activating stimulus was not endotoxin. Extensive rinsing of the module with water before extract preparation totally mitigated the in-vitro production of interleukin-1. Our results suggest that the extract-induced activation of peripheral blood mononuclear cells found with some dialysers containing membranes of cellulosic origin cannot be exclusively related to the membrane polymer, but depends on a number of other parameters such as sterilisation and storage mode of a given membrane.