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 refractory to priming by tumor necrosis factor-alpha (TNF alpha). Soluble TNF alpha binding protiens (sTNFR) accumulate in the plasma of azotemic patients. To test the hypothesis that these increased sTNFR concentrations inhibit TNF alpha priming of oxidative burst activity, we measured plasma sTNFR concentrations in nondialyzed azotemic patients, hemodialysis patients, and normal subjects, and determined TNF alpha priming of fMet-Leu-Phe-stimulated superoxide production in neutrophils incubated in plasma with differing levels of sT-NFR. These sTNFR concentrations increased significantly as creatinine clearance decreased and were significantly greater in hemodialysis patients than could be accounted for by loss of renal function alone. TNF alpha primed superoxide production by normal neutrophils in normal plasma, but this effect was significantly reduced in plasma with increased concentrations of sTNFR. Neutrophils from azotemic and hemodialysis patients were refractory to priming by TNF alpha in autologous plasma, and incubation in normal plasma only partially corrected this defect. We conclude that sTNFR accumulate as a result of the loss of renal function and hemodialysis and inhibit TNF alpha priming of neutrophils in azotemic and hemodialysis patients, but that these cells also have an intrinsic functional defect.
Ward
R
R
Department of Medicine, School of Medicine, University of Louisville, Kentucky 40292, USA.
McLeish
K R
KR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D012044:Regression Analysis; D006435:Renal Dialysis; D016897:Respiratory Burst; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014511:Uremia / Q000097:blood / Q000628:therapy
D015703:Antigens, CD; D001798:Blood Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine