In vivo induction of interleukin-1 during hemodialysis

Abstract

In vivo induction of interleukin-1 (IL-1) production during hemodialysis was investigated by measuring IL-1 activity in monocyte lysates from 59 patients undergoing long-term maintenance hemodialysis with complement activating and non-complement activating devices. In patients dialyzed with new hollow-fiber cuprophane dialyzers, predialytic (T0) monocyte-associated IL-1 activity was 12.5 ± 3.0 U/ml (mean ± SEM), a value that was higher than that found in normal individuals (2.85 ± 0.85 U/ml; P < 0.025) and in non-dialyzed patients with chronic renal failure (0.95 ± 0.85 U/ml, P < 0.0001). Cell-associated IL-1 activity was consistently increased after five hours of dialysis with cuprophane membranes (42.4 ± 5.5 U/ml, P < 0.0005). Systemic complement activation was demonstrated by the finding of increased plasma levels of C3adesArg antigen during dialysis. In patients dialyzed with high permeability polyacrylonitrile and polysulfone membranes, no intradialytic change in cell-associated IL-1 and no complement activation occurred. However, the mean predialytic values of monocyte-associated IL-1 in these patients (that is, 32.9 ± 5.6 U/ml and 38 ± 5.65 U/ml for the polyacrylonitrile and the polysulfone groups, respectively) were higher than the predialytic levels of cell-associated IL-1 in the patients from the cuprophane group (P < 0.0025). Monocytes obtained at the beginning and five hours of dialysis from patients dialyzed with polyacrylonitrile devices, and monocytes obtained at five hours but not at the beginning of dialysis from patients dialyzed with cuprophane membranes, spontaneously released extracellular IL-1 after 24 hours of culture in serum free conditions. Neither polyacrylonitrile nor cuprophane differed in their capacity to stimulate monocytes that had adhered to the membrane, to produce IL-1 in serum free cultures. These results indicate that IL-1 is transiently generated during hemodialysis with complement activating membranes when C3a/C3adesArg and C5a/C5adesArg, which are known inducers of IL-1 production, are generated in plasma. Non-complement dependent factors, possibly LPS or fragments of LPS that often contaminate bicarbonate dialysates, may be responsible for chronic stimulation of IL-1 production in patients dialyzed with high permeability membranes.