Tumor necrosis factor-α, interleukin-1β, and interleukin-1 receptor antagonist in dialysate and serum from patients on continuous ambulatory peritoneal dialysis

Abstract

Dialysate and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-1ra were investigated in 20 patients on continuous ambulatory peritoneal dialysis (CAPD), who altogether had 30 episodes of peritonitis. Bacterial growth was found in 25 (83%) of the dialysate samples. Staphylococcus epidermidis was the single most common microorganism, found in 44% of the culture-verified peritonitis. Samples from dialysate bags were obtained during the first month of dialysis and during peritonitis from the first three bags on day 1 (the day of admittance) and from nightbags on days 3 and 10. Serum samples were drawn on days 1 and 10. The peak concentrations of cytokines occurred on the first day of infection. In dialysates, TNF-α was elevated in 96% of the patients, with a peak median concentration of 160 pg/mL (range, <15 to 4,400 pg/mL). Seventy-five percent of the dialysates had elevated IL-1β, with the highest median level of 52 pg/mL (range, <10 to 940 pg/mL), whereas all patients had elevated IL-1ra, with a peak median value of 10,300 pg/mL (range, 470 to 79,000 pg/mL). TNF-α, IL-1β, and IL-1ra were significantly higher than in corresponding noninfected samples (TNF-α median value, <15 pg/mL; IL-1β, <10 pg/mL; and IL-1ra, 150 pg/mL; P <0.0001, P <0.002, and P <0.001, respectively). In serum, elevated TNF-α levels were found in 92% of the episodes, but the median levels were less than one third of the corresponding lavage levels, IL-1β was detected in 8% of the episodes and, although IL-1ra was found in 92% of the patients, the dialysate levels were more than 15 times higher. In dialysate, a correlation was observed for TNF-α and IL-1ra and also between IL-1β and IL-1ra. IL-1β and IL-1ra also correlated with the previously analyzed IL-6, and IL-1β correlated with the previously analyzed IL-8. Patients infected with high virulent strains had higher cytokine levels as compared with those infected with low virulent strains. In conclusion, our study shows markedly elevated TNF-α, IL-1β, and IL-1ra levels in the acute stage in CAPD patients with peritonitis.