N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients.
OBJECTIVE
The antioxidant N-acetylcysteine (NAC) has been shown to attenuate septic tissue injury. To evaluate whether NAC affects host defense mechanisms in critically ill patients, thus predisposing to increased risk of infection, the current study focuses on neutrophil phagocytotic and burst activity after treatment with NAC.


METHODS
Prospective, randomized, clinical trial.


METHODS
Twelve-bed operative intensive care unit in a university hospital.


METHODS
Thirty patients diagnosed with sepsis/systemic inflammatory response syndrome, or multiple trauma.


METHODS
Patients were randomly assigned to receive either NAC (n = 15) 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 NAC (3 x 300 mg/day [control]; n = 15), respectively.


RESULTS
Blood samples were taken before NAC high-dose infusion (day 1), after increasing doses of NAC (days 3 and 5) and 4 days after the last high-dose treatment (day 8). Neutrophil oxidative burst activity after stimulation with Escherichia coli and polymorphonuclear phagocytosis were determined in a flow cytometric assay. Baseline values of polymorphonuclear functions were comparable in both groups. NAC high-dose treatment resulted in a significantly improved phagocytosis activity compared with control patients. In contrast to this, polymorphonuclear burst activity was significantly reduced in the NAC high-dose treated group on day 3.


CONCLUSIONS
These findings suggest that infusion of NAC in high doses affects granulocyte functions in critically ill patients. Antimicrobial host defense requires the effective sequence of cell adhesion, phagocytosis, and bactericidal 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.
Heller
A R
AR
Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Dresden, Germany. heller-a@rcs.urz.tu-dresden.de
Groth
G
G
Heller
S C
SC
Breitkreutz
R
R
Nebe
T
T
Quintel
M
M
Koch
T
T
D018806:APACHE; D000111:Acetylcysteine / Q000494:pharmacology* / Q000627:therapeutic use*; D000328:Adult; D000704:Analysis of Variance; D005260:Female; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D007262:Infusions, Intravenous; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D011446:Prospective Studies; D016897:Respiratory Burst / Q000187:drug effects* / Q000276:immunology; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016019:Survival Analysis; D013997:Time Factors
D016166:Free Radical Scavengers; D000111:Acetylcysteine