Role of different dialysis membranes in the release of interleukin-6-soluble receptor in uremic patients

Background. Interleukin-6(IL-6) exerts its actions through a cell-surface r eceptor system that consists of two transmembrane subunits: the IL-6 bindin g glycoprotein gp 80 (IL-6R) and the signal-transducing; component (gp 130) . Soluble forms of the IL-6R (sIL-GR) are generated by shedding of the memb rane-associated proteins, The sIL-6R binds the ligand IL-6 with comparable affinity as the membrane-associated IL-6R and enhances the actions of IL-6. Methods. Our aim was to evaluate the role of both uremia and different dial ysis membranes on peripheral blood mononuclear cell (PBMC) release (either in absence or in presence of mitogon stimulation) and plasma Levels of sIL- 6R. Ten patients chronically dialyzed with cuprophan membranes (CU), eight patients on regular dialysis treatment with polymethylmethacrylate (PMMA) m embranes, 11 uremic nondialyzed patients (UR), and 12 healthy subjects (CON ) were included in the study. Results. PBMCs harvested from CU spontaneously released significantly (P < 0.01) greater amounts of sIL-6R (881.8 +/- 80.1 pg/mL), as compared with CO N (267.5 +/- 26.5 pg/mL), UR (258.4 +/- 38.1 pg/mL), and PMMA (288.4 +/- 24 .6 pg/mL). Under mitogenic stimulation, the sIL-6R release was significantl y (P < 0.01) increased in all groups. The greater PBMC production of sIL-6R in CU was followed by significantly (P < 0.01) higher levels of circulatin g soluble receptors (48.7 +/- 2.5 ng/mL, 60%), as compared with CON (30.5 /- 1.9 ng/mL). UR also showed high circulating levels of sIL-6R (53.3 +/- 5 .9 ng/mL), probably secondary to an impaired, urinary excretion. Circulatin g levels of sIL-6R in PMMA were comparable to CON (30.3 +/- 3.3 ng/mL). Eit her the absence of monocyte activation or the adsorption of sIL-6R on the h ydrophobic PMMA surface could explain this finding. Conclusions. These results suggest an important role for poor dialysis bioc ompatibility of CU on the release of sIL-6R, which increases sIL-6R plasma levels, thereby enhancing the inflammatory effects of IL-6.