The Tumor Necrosis Factor (TNF)-C( system in organ failure and transplantation

Patients on hemodialysis suffer from an impaired immunity against infectious agents, hyporesponsiveness to vaccination and are prone to develop malignancies. This clinical state of immunoincompetence may be due to a unbalance in their defense mechanisms in which TNF-o: and its soluble receptors I and 2 playa central role. We measured, with double-sandwich ELISA, the levels of TNF-a and the soluble TNF-receptors in pelipheral blood of patients on chronic intermittent hemodialysis (CIHD), on peritoneal dialysis (CAPD) and pre-dialysis end-stage renal failure (ESRF). Using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) analysis, we quantified the amount of TNF-a mRNA in peripheral blood mononuclear cells (PBMC) obtained from these patient groups. In none of the patient groups elevated levels of TNF -a were detected with ELISA, while high levels of soluble TNF'-receptors were present in ESRF, CAPD and CIHD patients. This may be the result of an activated TNF-a system or due to their impaired renal clearance. TNF-a mRNA level was elevated in CIHD patients compared to ESRF and CAPD patients or healthy controls. This suggests that only during chronic HD the TNF-o: system is activated. High levels of sTNFR, found in ESRF or CAPD patients do not reflect activation of TNF -a system, but are the result of impaired renal clearance of the receptors. Indeed, we found a strong linear correlation between the levels of sTNF receptors and renal function. Nevertheless, these high levels of sTNF-receptors are biological active, as they were able to bind active TNF-a up to 75% (range 46-83%) and thus inhibit the bioactivity and bioavailability of produced TNF-a. This may playa role in the immunoincompetence of these patients.