The TNF-alpha system in heart failure and after heart transplantation: plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity
BACKGROUND: The two soluble tumour necrosis factor (TNF) receptors (sTNF-R1, sTNF-R2) can bind TNF-alpha, which is a cytokine with cardiodepressant properties. In heart failure and after heart transplantation, the TNF-alpha system is unbalanced, due to elevated levels of sTNF receptors. AIM: To assess the activity of the TNF-alpha system in patients with heart failure and after heart transplantation. METHODS: We measured TNF-alpha mRNA expression of peripheral blood mononuclear cells, plasma levels of TNF-alpha and sTNF reverse transcriptase receptors, using polymerase chain reaction and ELISA and performed a TNF-alpha binding capacity analysis, quantitating the buffer capacity of patients' plasma. RESULTS: In 11 patients with heart failure and in 15 cardiac allograft recipients, the TNF-alpha mRNA expression was comparable to controls. This level of mRNA was not accompanied by detectable TNF-alpha plasma levels. Significantly higher sTNF receptors levels were found in patients: ( P <0.001; ANOVA). The TNF-alpha binding capacity of patients' plasma was significantly increased, which led to decreased TNF-alpha recovery ( P<0.05). Both sTNF receptors showed a linear correlation with serum creatinine (sTNF-RI: r=0.92; sTNF-R2: r=0.82, P<0.001). CONCLUSIONS:The TNF-alpha mRNA expression and plasma levels show that the 'peripheral' TNF-alpha system is not activated. The high sTNF-receptors levels and their elevated TNF-alpha binding capacity, resulting in decreased TNF-alpha bioavailability, may contribute to an immunosuppressed state in these patients.
|Keywords||Adult, Aged, Biological Availability, Creatinine/blood, Enzyme-Linked Immunosorbent Assay, Female, Heart Failure, Congestive/*metabolism, Heart Transplantation/*physiology, Humans, Male, Middle aged, RNA, Messenger/*metabolism, Receptors, Tumor Necrosis Factor/blood/genetics/*metabolism, Solubility|
van Riemsdijk-van Overbeeke, I.C., Baan, C.C., Niesters, H.G.M., Hesse, C.J., Loonen, E.H., Weimar, W., … Maat, A.W.P.M.. (1999). The TNF-alpha system in heart failure and after heart transplantation: plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity. European Heart Journal, 20(11), 833–840. Retrieved from http://hdl.handle.net/1765/9102