THE EFFECT OF UREMIA ON TUMOR-NECROSIS-FACTOR-ALPHA RELEASE AFTER AN IN-VITRO WHOLE-BLOOD ENDOTOXIN CHALLENGE

Uremia has been associated with immunologic aberrations, including ane rgy, increased susceptibility to infections, and reduced phagocytic ac tivity of polymorphonuclear leukocytes. In this study, cytokine releas e in uremic and nonuremic blood after in vitro endotoxin stimulation w as studied. Blood from nonuremic controls, chronic renal failure patie nts not on dialysis, and chronic hemodialysis patients predialysis and postdialysis was spiked with 10 ng/mL of Escherichia coli endotoxin a nd incubated for 2 and 26 h. Plasma tumor necrosis factor-alpha (TNFal pha) concentrations were determined by ELISA after each incubation per iod. To further study which uremic blood component may be responsible for enhanced release of TNFalpha, plasma and cellular components of ch ronic renal failure patients and controls were switched and then given an in vitro endotoxin stimulation (1 ng/mL). It was found that (1) TN Falpha release is enhanced by uremia and is exacerbated with progressi ve declines in renal function, (2) enhanced TNFalpha release is relate d to a blood cellular phenomenon induced by uremia, and (3) enhanced T NFalpha release in hemodialysis patients is associated with a prolonge d stimulation and/or reduced plasma elimination of TNFalpha.