Copyright © 1999 by the European Society of Cardiology.
The TNF-
system in heart failure and after heart transplantation; plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity
Department of Internal Medicine I, Virology and Thorax Center, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands
revised November 30, 1998; and accepted Dember 2, 1998
Abstract
Background The two soluble tumour necrosis factor (TNF) receptors (sTNF-R1, sTNF-R2) can bind TNF-
, which is a cytokine with cardiodepressant properties. In heart failure and after heart transplantation, the TNF- system is unbalanced, due to elevated levels of sTNF receptors.
Aim To assess the activity of the TNF- system in patients with heart failure and after heart transplantation.
Methods We measured TNF-mRNA expression of peripheral blood mononuclear cells, plasma levels of TNF- and sTNF reverse transcriptase receptors, using polymerase chain reaction and ELISA and performed a TNF- 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- mRNA expression was comparable to controls. This level of mRNA was not accompanied by detectable TNF-plasma levels. Significantly higher sTNF receptors levels were found in patients: (P<0·001; ANOVA). The TNF-binding capacity of patients’ plasma was significantly increased, which led to decreased TNF-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-mRNA expression and plasma levels show that the ‘peripheral’ TNF-system is not activated. The high sTNF-receptors levels and their elevated TNF-binding capacity, resulting in decreased TNF- bioavailability, may contribute to an immunosuppressed state in these patients.
Key Words: TNF- • soluble TNF receptors • heart failure • heart transplantation
f1 Correspondence: I. C. van Riemsdijk-van Overbeeke, Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
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