N-acetyl-l-cystine (NAC) protects against H9N2 swine influenza virus-induced acute lung injury

Int Immunopharmacol. 2014 Sep;22(1):1-8. doi: 10.1016/j.intimp.2014.06.013. Epub 2014 Jun 24.

Abstract

The antioxidant N-acetyl-l-cysteine (NAC) had been shown to inhibit replication of seasonal human influenza A viruses. Here, the effects of NAC on H9N2 swine influenza virus-induced acute lung injury (ALI) were investigated in mice. BALB/c mice were inoculated intranasally with 10(7) 50% tissue culture infective doses (TCID(50)) of A/swine/HeBei/012/2008/(H9N2) viruses with or without NAC treatments to induce ALI model. The result showed that pulmonary inflammation, pulmonary edema, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6, IL-1β and CXCL-10 in BALF were attenuated by NAC. Moreover, our data showed that NAC significantly inhibited the levels of TLR4 protein and TLR4 mRNA in the lungs. Pharmacological inhibitors of TLR4 (E5564) exerted similar effects like those determined for NAC in H9N2 swine influenza virus-infected mice. These results suggest that antioxidants like NAC represent a potential additional treatment option that could be considered in the case of an influenza A virus pandemic.

Keywords: Acute lung injury; H9N2 swine influenza virus; N-acetyl-l-cystine (NAC); Toll-like receptor 4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Acute Lung Injury / etiology
  • Acute Lung Injury / immunology*
  • Acute Lung Injury / prevention & control
  • Animals
  • Antioxidants / administration & dosage*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammation Mediators / metabolism
  • Influenza A Virus, H9N2 Subtype / drug effects
  • Influenza A Virus, H9N2 Subtype / physiology*
  • Influenza, Human / drug therapy
  • Influenza, Human / immunology*
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives
  • Lipid A / pharmacology
  • Lung / drug effects
  • Lung / immunology*
  • Lung / virology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / complications
  • Orthomyxoviridae Infections / drug therapy
  • Orthomyxoviridae Infections / immunology*
  • Peroxidase / metabolism
  • Swine
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Virus Replication / drug effects

Substances

  • Antioxidants
  • Cytokines
  • E5564
  • Inflammation Mediators
  • Lipid A
  • Toll-Like Receptor 4
  • Peroxidase
  • Acetylcysteine