INCREASED LEVELS OF SERUM NEOPTERIN AND DECREASED PRODUCTION OF NEUTROPHIL SUPEROXIDE ANIONS IN CHRONIC HEART-FAILURE WITH ELEVATED LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA

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-l, interleukins, 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 U-myristate If-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.