Appearance of tumor necrosis factor-alpha and soluble TNF-receptors I and II in peritoneal effluent of CAPD.

Dialysate and serum concentrations of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-receptor I (sTNFRI) and soluble TNF-receptor II (sTNFRII) were measured during stable and infectious CAPD to determine whether these mediators are released intraperitoneally or derived from the circulation. Dialysate/serum ratios were compared to those of various marker proteins for peritoneal transport and to interleukin-6 (IL-6), which is locally produced. Peritoneal immunoreactive TNF-alpha could be detected in 19 of 20 stable CAPD patients after a night dwell, but only occasionally and in lower concentrations during and after a standard four-hour peritoneal permeability test. Both sTNFRs highly exceeded TNF-alpha dialysate concentrations. In case of peritonitis a median 16-fold increase in dialysate TNF-alpha occurred on the first day, which declined towards control values during a longitudinal follow-up of eight consecutive days. sTNFRI and sTNFRII in dialysate increased three- to fourfold. Their peaks, however, appeared on the second peritonitis day. Bioactive TNF-alpha was only detected when immunoreactive levels exceeded 1000 pg/ml. Serum values of all variables were not altered during infection; sTNFRs exceeded TNF-alpha 300- to 400-fold. During stable CAPD indirect evidence was obtained for transperitoneal transport from plasma to dialysate of TNF-alpha (molecular wt 17 kD), sTNFRI (55 kD) and sTNFRII (75 kD). Dialysate/serum (D/S) ratios were higher, the lower the molecular weight; they were related to D/S ratios of those marker proteins with the nearest molecular weight; D/S ratios were unrelated to the intraperitoneally produced IL-6. Furthermore, the observed D/S ratios were as expected theoretically for their molecular weights.(ABSTRACT TRUNCATED AT 250 WORDS)