Soluble tumor necrosis factor receptors are increased in hemodialysis patients

Tumor necrosis factor-alpha (TNF alpha) interacts with cells through specific membrane receptors. Exposure to agonists, such as C5a, causes cells to shed these receptors, forming soluble TNF alpha binding proteins (sTNFR). Because cellulose membranes activate complement, we tested the hypothesis that dialysis with these membranes contributes to the increased levels of sTNFR observed in hemodialysis patients. sTNFR levels were measured pre- and post-dialysis in patients treated with dialyzers containing new cellulose membranes. Plasma sTNFR concentrations were markedly increased pre-dialysis, compared with normal (38.3 +/- 13.5 ng/ml versus 2.1 +/- 0.7 ng/ml), and increased further during dialysis, even after post-dialysis concentrations were corrected for hemoconcentration. We examined the impact of the increased sTNFR levels on the ability of TNF alpha to prime neutrophil superoxide production in cross-incubation experiments. When normal neutrophils were incubated with TNF alpha in the presence of hemodialysis patient plasma, the resulting increase in fMLP stimulated superoxide production was significantly less than when normal plasma was used. Incubation of hemodialysis patient neutrophils in normal plasma only partly restored their ability to be primed by TNF alpha, suggesting an intrinsic functional defect in these cells, in addition to the effects of sTNFR. Our results suggest that dialysis with cellulose membranes contributes to the increased levels of sTNFR observed in dialysis patients, and that these concentrations are sufficient to impair the normal actions of TNF alpha.