SOLUBLE TNF-ALPHA RECEPTORS ARE INCREASED IN CHRONIC RENAL-INSUFFICIENCY AND HEMODIALYSIS AND INHIBIT NEUTROPHIL PRIMING BY TNF-ALPHA

The oxidative burst of neutrophils from azotemic patients is refractor y to priming by tumor necrosis factor-alpha (TNF alpha). Soluble TNF a lpha binding proteins (sTNFR) accumulate in the plasma of azotemic pat ients. To test the hypothesis that these increased sTNFR concentration s inhibit TNF alpha priming of oxidative burst activity, we measured p lasma sTNFR concentrations in nondialyzed azotemic patients, hemodialy sis patients, and normal subjects, and determined TNF alpha priming of fMet-Leu-Phe-stimulated superoxide production in neutrophils incubate d in plasma with differing levels of sTNFR. These sTNFR concentrations increased significantly as creatinine clearance decreased and were si gnificantly greater in hemodialysis patients than could be accounted f or by foss of renal function alone. TNF alpha primed superoxide produc tion by normal neutrophils in normal plasma, but this effect was signi ficantly reduced in plasma with increased concentrations of sTNFR. Neu trophils from azotemic and hemodialysis patients were refractory to pr iming by TNF alpha in autologous plasma, and incubation in normal plas ma only partially corrected this defect. We conclude that sTNFR accumu late as a result of the loss of renal function and hemodialysis and in hibit TNF alpha priming of neutrophils in azotemic and hemodialysis pa tients, but that these cells also have an intrinsic functional defect.