Increased levels of serum neopterin and decreased production of neutrophil superoxide anions in chronic heart failure with elevated levels of tumor necrosis factor-alpha

Department of Internal Medicine, University of Innsbruck, Austria.

OBJECTIVES. The purpose of this study was to examine the role of tumor necrosis factor-alpha and tetrahydrobiopterin and superoxide anion release from neutrophils in severe chronic heart failure. BACKGROUND. Previous studies have demonstrated elevated production of tumor necrosis factor-alpha and free radical-induced endothelial cell damage in severe heart failure. METHODS. Plasma and serum levels of immunoreactive interleukin-1, interleukin-6, interferon-gamma, neopterin and tumor necrosis factor-alpha and the release of superoxide anions from circulating neutrophils both at basal conditions and after triggering with f-Met-Leu-Phe or phorbol 12-myristate 13-acetate were measured in 16 patients with severe heart failure and in 11 healthy control subjects. RESULTS. Circulating levels of tumor necrosis factor-alpha and neopterin were elevated in patients with heart failure compared with values in control subjects. A significant correlation between the two was found. Basal and phorbolester-triggered release of oxygen radicals from neutrophils was not affected in patients with heart failure. However, formylpeptide-stimulated release of oxygen radicals by neutrophils was significantly reduced. CONCLUSIONS. Suppressed neutrophil function in patients with heart failure exhibiting elevated levels of tumor necrosis-alpha factor may indicate self-protection against the deleterious effects of neutrophil-derived oxygen radicals. Through induction of tetrahydrobiopterin synthesis (as reflected by increased neopterin), tumor necrosis factor-alpha may affect nitric oxide synthesis.

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