Synergetic effect of dialyzer membrane and lipopolysaccharide on peripheral blood mononuclear cell cytokine production in uremic patients

Objective To investigate the effect of lipopoly-saccharide(LPS) and dialyze r membrane on cytokine gene expression and protein production in uremic pat ients on continuous ambulatory peritoneal dialysis (CAPD) and regular hemod ialysis(HD). Methods Interleukin-1 beta (IL-1 beta) and interleukin-1 receptor antagonis t (lL-1Ra) produced by cultured peripheral blood mononuclear cells (PBMC) a fter exposure to cuprammonium ( Cup) membrane, polysulfone ( PS) membranes or endotoxin were detected using enzyme-linked immunoabsorbent assay. MRNA expression was determined simultaneously by in situ hybridiztion. Results In the absence of endotoxin, a small amount of IL-1 beta and IL-1Ra was produced by PBMC harvested from HD and CAPD patients after incubation with Cup or PS during subsequent 24-hour culture. For healthy controls, IL- 1 beta was barely detectable just above the detection limit. Although no di fferences could be found in protein synthesis between Cup and PS, in situ h ybridization showed that Cup induced markedly higher level mRNA coding,for IL-1 beta and IL-1Ra. In contrast, when subsequently stimulated with endoto xin, PBMC incubated with Cup could produce significantly larger amount of I L-1P and IL-1Ra compared with either unstimulated cells or postincubation P BMC with PS. LPS-stimulated PBMC in healthy subjects produced similar amoun t of IL-1P and markedly lower IL-1Ra as compared with uremic patients on HD and CAPD. Conclusions Two steps are required in healthy control for IL-1 beta and IL- 1Ra production: induction of mRNA transcription by membrane contact, follow ed by LPS-induced translation, while in uremic patients on HD or CAPD bioin compatibility-membrane and LPS have a synergetic effect on IL-1 beta and IL -1Ra production. There exists an unbalance between IL-1 beta and its specif ic inhibitor in maintenance dialysis patients .