Effect of N-acetylcysteine on neutrophil activation markers in healthy volunteers: In vivo and in vitro study

• Published in: Pharmacological research Vol. 53; no. 3; pp. 216 - 225
• Main Authors: Sadowska, Anna M., Manuel-y-Keenoy, Begoña, Vertongen, Tim, Schippers, Glenn, Radomska-Lesniewska, Dorota, Heytens, Elke, De Backer, Wilfried A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-03-2006
• Subjects: Acetylcysteine - pharmacology; Adult; Chemotaxis, Leukocyte; Dose-Response Relationship, Drug; Female; Glutathione; Humans; In Vitro Techniques; Interleukin-8 - metabolism; Male; Middle Aged; N-Acetylcysteine; Neutrophil Activation; Neutrophils - drug effects; Neutrophils - enzymology; NF-kappa B - metabolism; Pancreatic Elastase - metabolism; Respiratory Burst; Time Factors; Neutrophil activation; Respiratory burst; N-Acetylcysteine; Glutathione
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2005.11.003

Neutrophil activation is implicated in the pathogenesis of inflammatory processes such as chronic obstructive pulmonary disease (COPD). We wished to evaluate both in vivo and in vitro whether
N-acetylcysteine (NAC) has an effect on the response of activated neutrophils.
Ten healthy volunteers took NAC (600
mg
daily) for 14 days. The effects on basal and fMLP-induced respiratory burst and chemotaxis were assessed at baseline, 2
h and 14 days after NAC intake. Neutrophils from healthy volunteers (NAC naïve) were pre-incubated with NAC for 30
min and the effects on the release of elastase and IL-8, the respiratory burst in response to fMLP and PMA, on TNFα-induced NFκB activation and on the migration across an endothelial–epithelial bilayer were investigated.
PMA and fMLP-induced neutrophil respiratory burst and chemotaxis were lower after 14 days of NAC intake but not after 2
h. In vitro incubation with NAC inhibited release of elastase (
p
<
0.05), IL-8 (
p
<
0.05), respiratory burst and NFκB activation at 10
mM but not at lower concentrations. This was accompanied by a decrease in cellular ATP content.
Our results suggest that acute in vitro addition of NAC can modulate neutrophil activity only when used at the high concentrations which directly affect cellular metabolism. On the other hand, the lower doses of NAC given in vivo might require longer times in order to achieve sustained effects on the cellular thiols which lead to changes in the redox status.