Neutrophil superoxide release and interleukin 8 in acute myocardial infarction: distinction between complicated and uncomplicated states

Superoxide release in neutrophils and sera levels of interleukin 8 (IL-8) were determined in 15 patients with complicated acute myocardial infarction (MI) and 15 patients with uncomplicated MI. All patients showed increased superoxide release in unstimulated and stimulated neutrophils compared with healthy control subjects, indicating priming of these cells. Superoxide release of unstimulated or stimulated neutrophils was found to be significantly higher in patients with complicated MI than in patients with uncomplicated MI. Thrombolytic therapy did not affect the rates of superoxide release. The neutrophil chemoattractant/activator IL-8 was detected in the sera of all patients, with significantly higher levels in those with complicated MI. The highest levels of IL-8 were detected at admission to the Coronary Care Unit and significantly decreased thereafter, suggesting its contribution to neutrophil-mediated tissue injury. The high levels of IL-8 may be one of the major contributors to the priming of neutrophils in these patients.     

Inhibited neutrophil functions in patients treated with nifedipine but not with verapamil or diltiazem

Neutrophil functions were studied in patients receiving calcium channel blockers: nifedipine, diltiazem or verapamil. Neutrophils from patients treated with nifedipine showed a significantly lower superoxide generation stimulated by phorbol myristate acetate (PMA) (50 ng mL⁻¹), opsonized zymosan (1 mg mL⁻¹) or formyl-methionyl-leucyl-phenylalanine (FMLP) (10⁻⁷  m ), whereas superoxide generation by neutrophils of patients receiving diltiazem or verapamil showed only a slight and insignificant reduction compared with controls. Similarly, chemotaxis towards 10⁻⁷  m FMLP and phagocytosis were significantly lower in patients receiving nifedipine compared with controls and were only slightly reduced in patients receiving diltiazem or verapamil. Nifedipine was the most efficient drug in inhibiting the rise in intracellular calcium ion concentration ([Ca²⁺]_i) when added in vitro and in neutrophils of patients receiving this drug, whereas verapamil had no significant effect. The correlation between the inhibitory effect of nifedipine on neutrophil function and the elevation of [Ca²⁺]_i suggests that nifedipine inhibits neutrophil functions through its effect on [Ca²⁺]_i. However, it is not the sole mechanism as superoxide generation induced by PMA, an agent that does not induce a rise in [Ca²⁺]_i, is also inhibited. The unique effect of nifedipine in reducing neutrophil functions in vivo suggests its clinical implications concerning response to acute ischaemic myocardial events.     

SUCCESSFUL TREATMENT OF A PATIENT WITH RECURRENT FURUNCULOSIS BY VITAMIN C: IMPROVEMENT OF CLINICAL COURSE AND OF IMPAIRED NEUTROPHIL FUNCTIONS

Background. Neutrophils play a critical role in host defense against a variety of microbial pathogens. There is much information to suggest a role for vitamin C in the physiology of neutrophils. Thus, the effects of vitamin C treatment were studied in a patient with a history of recurrent furunculosis who showed altered neutrophil functions. Methods. Superoxide generation was measured by cytochrome C reduction. Phagocytosis of opsonized zymosan by neutrophils and chemotaxis on agarose plates were determined. Results. Chemotaxis, phagocytosis, and superoxide generation of the patient's neutrophils were significantly lower than those of the matched control. Treatment with vitamin C (500 mg/day) for 30 days caused a dramatic clinical response and a significant improvement of all three neutrophil functions to values similar to those of the controls. Conclusions. We suggest that the patient described here had a temporary defect in neutrophil functions. The treatment with vitamin C probably prevented neutrophil oxidation, thus contributing to recovery of neutrophil function and arrest of furunculosis.