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- Title
Appearance of tumor necrosis factor-α and soluble TNF-receptors I and II in peritoneal effluent of CAPD.
- Authors
Zemel, Désirée; Imholz, Alexander L. T.; de Waart, Dirk R.; Dinkla, Chris; Struijk, Dirk G.; Krediet, Raymond T.
- Abstract
Dialysate and serum concentrations of tumor necrosis factor-α (TNF-α), 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-α 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-α dialysate concentrations. In case of peritonitis a median 16-fold increase in dialysate TNF-α 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-α was only detected when immunoreactive levels exceeded 1000 pg/ml. Serum values of all variables were not altered during infection; sTNFRs exceeded TNF-α 300- to 400-fold. During stable CAPD indirect evidence was obtained for transperitoneal transport from plasma to dialysate of TNF-α (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. Higher than expected D/S ratios were found during peritonitis for TNF-α on days 1 and 2, and for sTNFRII on day 2, pointing to local release within the peritoneal cavity only in the acute inflammatory phase. Gel permeation chromatography revealed that TNF-α was present in a monomeric 17 kD form, unbound to receptors, whereas in case of peritonitis smaller sTNFRII fragments, transported at a higher rate, could not be excluded. Therefore, these higher than expected D/S ratios indicate local production of TNF-α during peritonitis and possibly also of sTNFRII, although transport of smaller receptor fragments might also occur.
- Subjects
TUMOR necrosis factors; CYTOKINES; GROWTH factors; INTERLEUKIN-6; COLLOIDS; BLOOD plasma; PERITONITIS; SERUM
- Publication
Kidney International, 1994, Vol 46, Issue 5, p1422
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1994.414