TNF-alpha: mRNA, plasma protein levels and soluble receptors in patients on chronic hemodialysis, on CAPD and with end-stage renal failure

Background: Patients on hemodialysis suffer from an impaired immunity again st infectious agents, hyporesponsiveness to vaccination and are prone to de velop malignancies. This clinical state of immunoincompetence may be due to a disbalance in their defense mechanisms in which TNF-alpha and its solubl e receptors 1 and 2 play a central role. Patients and methods: We measured, with double-sandwich ELISA, the levels of TNF-alpha and the soluble TNF-re ceptors in peripheral blood of patients on chronic intermittent hemodialysi s (CMD), on peritoneal dialysis (CAPD) and pre-dialysis end-stage renal fai lure (ESRF). Using reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we quantified the amount of TNF-alpha mRNA in peripheral blood m ononuclear cells (PBMC) obtained from these patient groups. Results: In non e of the patient groups, elevated levels of TNF-alpha were detected with EL ISA, while high levels of soluble TNF receptors were present in ESRF CAPD a nd CIHD patients. This may be the result of an activated TNF-alpha system o r due to their impaired renal clearance. TNF-alpha mRNA level was elevated in CMD patients compared to ESRF and CAPD patients or healthy controls. Con clusion: This suggests that only during chronic HD is the TNF-alpha system activated. High levels of sTNFR, found in ESRF or CAPD patients do not refl ect activation of TNF-alpha system, but are the result of impaired renal cl earance of the receptors. Indeed, we found a strong linear correlation betw een the levels of sTNF receptors and renal function. Nevertheless, these hi gh levels of sTNF receptors are biological active, as they were able to bin d active TNF-alpha up to 75% (range 46-83%) and thus inhibit the bioactivit y and bioavailibility of produced TNF-alpha. This may play a role in the im munoincompetence of these patients.