Interleukin-1 receptors and receptor antagonist in haemodialysis.

Abstract

Biological activity of interleukin-1 (IL-1) depends on the number and type of IL-1 receptors on target cells and on the amounts of its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1ra). Expression of IL-1 receptor was studied on the peripheral blood mononuclear cells of 20 end-stage renal-disease patients maintained by chronic haemodialysis by means of either polysulphone (10 patients) or cuprophane membranes (10 patients) and compared to that of normal controls. Plasma and cellular levels of IL-1ra and IL-1 beta were also measured. The proportion of monocytes expressing the IL-1 receptor was strikingly higher in haemodialysis patients than in the healthy population. This proportion further increased during haemodialysis with cuprophane but not with polysulphone. Expression of the IL-1 receptor on lymphocytes was very low in both controls and dialysed patients; in the latter there was no intradialytic variation. Plasma concentrations of IL-1 beta and IL-1ra were elevated in haemodialysis patients and undetectable in controls. Whereas plasma IL-1 beta decreased throughout haemodialysis, IL-1ra further increased, with no significant differences between the two membranes used. Total cellular IL-1 beta and IL-1ra were also higher in the patient group than in the healthy controls. A further increase of both IL-1 beta and IL-1ra was detected at the end of the haemodialysis session with any membrane. Monocytes of haemodialysis patients circulate in a state of activation, which makes them both producer and target of IL-1. Thus there is an autocrine upregulation of IL-1 production. Although IL-1ra levels are high, they are most likely to be expression of monocyte activation rather than represent effective inhibitors of IL-1 activity.