N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients

Objective: The antioxidant N-acetylcysteine (NAC) has been shown to attenua te septic tissue injury. To evaluate whether NAG affects host defense mecha nisms in critically ill patients, thus predisposing to increased risk of in fection, the current study focuses on neutrophil phagocytotic and burst act ivity after treatment with NAG. Design: Prospective, randomized, clinical trial. Setting: Twelve-bed operative intensive care unit in a university hospital. Patients: Thirty patients diagnosed with sepsis/systemic inflammatory respo nse syndrome, or multiple trauma. Interventions: Patients were randomly assigned to receive either MAG (n = 1 5) for 4 days in increasing dosages (day 1: 6 g; day 2: 12 g; days 3 and 4: 18 g) or a mucolytic basis dosage of NAG (3 x 300 mg/day [control]; n = 15 ), respectively. Measurements and Main Results: Blood samples were taken before NAC high-dos e infusion (day 1), after increasing doses of MAG (days 3 and 5) and 4 days after the last high-dose treatment (day 8),. Neutrophil oxidative burst ac tivity after stimulation with Escherichia coli and polymorphonuclear phagoc ytosis were determined in a flow cytometric assay. Baseline values of polym orphonuclear functions were comparable in both groups, NAC high-dose treatm ent resulted in a significantly improved phagocytosis activity compared wit h control patients. In contrast to this, polymorphonuclear burst activity w as significantly reduced in the NAG high-dose treated group on day 3, Conclusion: These findings suggest that infusion of NAG in high doses affec ts granulocyte functions in critically ill patients. Antimicrobial host def ense requires the effective sequence of cell adhesion, phagocytosis, and ba ctericidal respiratory burst. The enhanced phagocytotic activity might be a compensatory mechanism in states of impaired respiratory burst to maintain tissue sterility. For certain mechanisms of disease, the effects observed might be favorable (e.g., ischemia/reperfusion, endothelial cell activation ), for others (infection) this might be detrimental.