Abstract
Objective: Expression of inflammatory mediators is controlled in part at the transcriptional level via nuclear factor-kappaB. Inhibition of nuclear factor-kappaB activation may be beneficial in critically ill patients. N-acetylcysteine is an antioxidant that inhibits nuclear factor-kappaB activation in vitro. In this pilot study we investigated the effect of N-acetylcysteine on nuclear factor-kappaB activation and circulating cytokine and adhesion molecules in patients with sepsis.
Design: Prospective, randomized, double blind, placebo-controlled pilot trial.
Setting: Eight-bed intensive care unit in a university teaching hospital.
Patients: Twenty consecutive patients within 12 hrs of fulfilling the consensus criteria for sepsis.
Interventions: A bolus of 150 mg/kg N-acetylcysteine in 100 mL of 0.9% saline over 15 mins, then 50 mg/kg in 100 mL of 0.9% saline over 4 hrs as a loading dose, and then a maintenance infusion of 50 mg/kg in 200 mL of 0.9% saline over each 24-hr period for a total of 72 hrs, or an equivalent volume of saline.
Measurements and Main Results: Nuclear factor-kappaB activation was measured in mononuclear leukocytes using electrophoretic mobility shift assay, at baseline and 24, 48, 72, and 96 hrs later.
Activation decreased significantly in patients treated with N-acetylcysteine (p = .016) but not placebo and was significantly reduced at 72 hrs compared with both preinfusion values (p = .028) and patients receiving placebo (p = .01). Plasma interleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 concentrations were measured using enzyme immunoassay. Interieukin-6 concentrations were high initially and then decreased in all patients, regardless of whether they received N-acetylcysteine or placebo. Interleukin-8 decreased significantly only in those who received N-acetylcysteine (p = .0081). Soluble intercellular adhesion molecule-1 concentrations remained unchanged in all patients.
Conclusions: Administration of N-acetylcysteine results in decreased nuclear factor-kappaB activation in patients with sepsis, associated with decreases in interleukin-8 but not interieukin-6 or soluble intercellular adhesion molecule-1. These pilot data suggest that antioxidant therapy with N-acetylcysteine may be useful in blunting the inflammatory response to sepsis. Further studies are warranted.
Original language | English |
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Pages (from-to) | 2574-2578 |
Number of pages | 4 |
Journal | Critical Care Medicine |
Volume | 31 |
Issue number | 11 |
DOIs | |
Publication status | Published - 2003 |
Keywords
- sepsis
- nuclear factor-kappa B
- N-acetylcysteine
- interleukin-6
- interleukin-8
- intercellular adhesion molecule-1
- antioxidant
- glutathione
- transcription factor
- FACTOR-KAPPA-B
- ACETYL-L-CYSTEINE
- FULMINANT HEPATIC-FAILURE
- HUMAN SEPTIC SHOCK
- ORGAN FAILURE
- DIMETHYL-SULFOXIDE
- GENE-TRANSCRIPTION
- LUNG INFLAMMATION
- PLASMA CYTOKINE
- DOUBLE-BLIND