Increased levels of serum neopterin and decreased production of neutrophil superoxide anions in chronic heart failure with elevated levels of tumor necrosis factor-alpha.
OBJECTIVE
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.
Wiedermann
C J
CJ
Department of Internal Medicine, University of Innsbruck, Austria.
Beimpold
H
H
Herold
M
M
Knapp
E
E
Braunsteiner
H
H
D009320:Atrial Natriuretic Factor / Q000097:blood; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019798:Neopterin; D009504:Neutrophils / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D001708:Biopterins; D019798:Neopterin; D009320:Atrial Natriuretic Factor; C003402:sapropterin