Inhibition of superoxide anion release from circulating neutrophils by L-arginine in man.

In animal studies of myocardial ischemia/reperfusion L-arginine reduces necrotic injury by preservation of endothelial function and attenuation of neutrophil accumulation in ischemic cardiac tissue. Because release of oxygen radical species by circulating neutrophils is important in endothelial function and ischemia-reperfusion injury, this study investigated the effect of intravenous administration of L-arginine on the in vitro release of superoxide anion of neutrophils in healthy young adults. Neutrophils were obtained at various time points before, during, and after infusion of L-arginine (17 mg kg-1 min-1 for 30 min) and analyzed for superoxide dismutase inhibitable reduction of ferricytochrome c. The spontaneously occurring respiratory burst of polymorphonuclear leukocytes at basal conditions was compared with that after triggering by 1 mumol/l formylpeptide or 50 ng/ml phorbolester. Infusion of L-arginine inhibited both basal (P < 0.01) and formylpeptide-triggered (P < 0.05) release of superoxide anion did, but not affect release stimulated by phorbol 12-myristate 13-acetate. Pretreatment of neutrophils with 1 mmol/l L-arginine in vitro also significantly reduced formylpeptide-triggered (1 mumol/l) superoxide anion release, suggesting that the affects observed after in vivo pretreatment may be due to direct action of L-arginine on neutrophils. These findings demonstrate the ability of L-arginine to reduce release of oxygen radical species by circulating neutrophils in man.

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-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.

[Coronary artery dilatation after infarct]. / Koronararteriendilatation nach Infarkt.

International studies (TAMI, TIMI II A, TIMI II B, European Cooperative Study, DANAMI, GUSTO, LATE, SWIFT, SAVE) confirmed the concept of coronary balloon angioplasty (PTCA) after acute myocardial infarction to be reduced to strict indications. These strict indications are on the one hand side based on anatomically suited coronary lesions, on the other hand side dependent on ischemia and/or angina. Direct (immediate) PTCA, rescue PTCA in evolving infarctions after failing lytic therapy are recommended, if operators and a well-trained team are available on a 24 hours basis. Routine PTCA after myocardial infarction is not save enough any time after myocardial infarction with or without lysis, therefore "watchful waiting" (Braunwald) still is recommended. But ischemia also depends on how much you look for it! The state of total occluded vessels, significant stenoses without ischemia, the elderly, non Q-wave infarctions, reduced left ventricular function are a field of discussion and patients with these findings should rather undergo angioplasty and PTCA, as long as we have no other detailed results from ongoing studies.

In vitro activation of neutrophils of the aged by recombinant human growth hormone.

Several functions of polymorphonuclear neutrophils (PMNL) have been found to be altered in the aged. As the neuroendocrine network, in particular growth hormone (GH), may interfere with the regulation of nonspecific host defense mechanisms, a recently described PMNL-priming activity of recombinant human (rH) GH in vitro was investigated. Oxidative metabolism of PMNL from young and old subjects was studied by measuring reduction of nitroblue tetrazolium (NBT) or cytochrome c. In the absence of stimulating agents, PMNL from old subjects reduced NBT to a significantly lesser extent than did PMNL from young subjects. Addition of rHGH to PMNL from old subjects reversed the suppressed spontaneous oxidative metabolism. No differences between young and old were observed for the increase of stimulated oxidative metabolism. The results suggest that altered PMNL function in the aged may be reversed by rHGH and that the ability of PMNL to respond to rHGH does not decline with age.

Priming of normal human neutrophils by recombinant human growth hormone.

Growth hormone (GH) plays an important role in the development, maintenance and function of the immune system. Previous data has demonstrated that GH is also a newly defined macrophage-activating factor. Activation of polymorphonuclear neutrophils (PMN) by GH has not yet been examined. This paper presents studies demonstrating the effects of GH on the migratory behaviour and respiratory burst of PMN. In a modified Boyden chamber chemotaxis assay, GH did not stimulate PMN locomotion when added directly to the cells but potently inhibited formylpeptide-stimulated chemotaxis with effective concentrations in the picomolar range. The migration inhibition observed is known from studies on PMN priming-factors to be due to enhanced adhesiveness of PMN to artificial surfaces such as nitrocellulose, suggesting that GH stimulates PMN adhesiveness. Priming of PMN by GH was confirmed by direct demonstration of a stimulatory effect on reduction of nitroblue tetrazolium. These findings suggest that GH may be involved in the regulation of PMN functions.