HIGH-CONCENTRATIONS OF SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTORS IN ASCITES

Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy-related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor-a concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy-related (p55: 26.0 +/- 8.6 ng/ml; p75: 20.5 +/- 17.4 ng/ml; mean +/- S.D.) and infected ascites (p55: 25.1 +/- 10.9 ng/ml, p75: 22.6 +/- 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 +/- 4.4 ng/ml; p75: 6.0 +/- 2.6 ng/ml). Patients with infected or malignancy-related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 +/- 15.2 ng/ml to 10.7 +/- 1.9 ng/ml and from 20.2 +/- 14.4 ng(ml to 7.5 +/- 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients. Levels of soluble tumor necrosis factor receptor p75 were also higher in ascites than in plasma in patients with malignant and infected ascites, but soluble tumor necrosis factor receptor p75 levels were usually higher in plasma than in ascites in patients with uncomplicated hepatic ascites. The concentrations of both tumor necrosis factor receptors correlated well in ascites (r = 0.83, p < 0.001) and plasma (r = 0.85, p < 0.001) but only weakly with tumor necrosis factor-alpha levels in ascites (p55: r = 0.32, p = 0.03; p75: r = 0.29, p = 0.047) and not with tumor necrosis factor-alpha in plasma. The high soluble tumor necrosis factor receptor concentrations found in ascites may influence the local bioavailability of tumor necrosis factor and might have an impact on the treatment of peritoneal carcinomatosis with recombinant tumor necrosis factor. Furthermore, the determination of soluble tumor necrosis factor receptors could be of value for the differential diagnosis of ascites.