In vivo antioxidant treatment suppresses nuclear factor-kappa B activation and neutrophilic lung inflammation

J Immunol. 1996 Aug 15;157(4):1630-7.

Abstract

We hypothesized that endotoxin injection in rats would stimulate in vivo nuclear factor-kappa B (NF-kappa B) activation in lung tissue and that antioxidant treatment before endotoxin injection would attenuate endotoxin-induced NF-kappa B activation, chemokine gene expression, and neutrophilic lung inflammation. We studied NF-kappa B activation in rat lung tissue following a single i.p. injection of endotoxin (6 mg/kg). After in vivo endotoxin treatment, lung NF-kappa B activation peaked at 2 h and temporally correlated with the expression of cytokine-induced neutrophil chemoattractant mRNA in lung tissue. Treatment with the antioxidant N-acetylcysteine (NAC) 1 h before endotoxin resulted in decreased lung NF-kappa B activation in a dose-dependent manner (from 200-1000 mg/kg) and diminished cytokine-induced neutrophil chemoattractant mRNA expression in lung tissue. Treatment with NAC significantly suppressed endotoxin-induced neutrophilic alveolitis. The average total lung lavage neutrophil count was 5.5 x 10(6) with endotoxin treatment vs 0.9 x 10(6) with NAC treatment before endotoxin. The NF-kappa B pathway represents an attractive therapeutic target for strategies to control neutrophilic inflammation and lung injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / pharmacology*
  • Acetylcysteine / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Base Sequence
  • Chemokines, CXC*
  • Chemotactic Factors / biosynthesis*
  • Chemotactic Factors / genetics
  • Chemotaxis, Leukocyte / drug effects
  • Dinoprost / analogs & derivatives
  • Dinoprost / biosynthesis
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Endotoxins / toxicity*
  • F2-Isoprostanes
  • Gene Expression Regulation / drug effects
  • Glutathione / biosynthesis
  • Glutathione / genetics
  • Growth Substances / biosynthesis*
  • Growth Substances / genetics
  • Inflammation
  • Intercellular Signaling Peptides and Proteins*
  • Leukocyte Count
  • Lung / drug effects
  • Lung / metabolism
  • Lung Diseases / etiology
  • Lung Diseases / immunology
  • Lung Diseases / prevention & control*
  • Male
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors*
  • Neutrophils / physiology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Distress Syndrome / drug therapy
  • Sepsis / chemically induced
  • Sepsis / complications

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Chemokines, CXC
  • Chemotactic Factors
  • Endotoxins
  • F2-Isoprostanes
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • NF-kappa B
  • RNA, Messenger
  • 8-epi-prostaglandin F2alpha
  • Dinoprost
  • Glutathione
  • Acetylcysteine