Oxidant tone regulates IL-8 production in epithelium infected with respiratory syncytial virus

Am J Respir Cell Mol Biol. 1995 Aug;13(2):237-44. doi: 10.1165/ajrcmb.13.2.7626291.


Respiratory syncytial virus (RSV) is an important respiratory pathogen that preferentially infects epithelial cells in the airway, and causes a local inflammatory response. Although it has been previously demonstrated that RSV-infected airway epithelial produce cytokines, including interleukin-8 (IL-8), which contributes to the inflammatory response, the regulation of this effect of RSV is unknown. To further characterize the mechanisms by which RSV infection triggers release of IL-8, we first exposed cultured A549 cells to RSV, and measured IL-8 release via enzyme-linked immunosorbent assays (ELISA), and IL-8 messenger RNA (mRNA) induction via Northern blot analysis. We observed a dose- and time-dependent release of IL-8 in response to RSV. The optimal dose of RSV was 10(4) TCID50/ml, and maximal release of IL-8 was measured at 72 to 96 h after infection. RSV induced a biphasic (early and late) increase in IL-8 mRNA. The early phase was independent of viral infection, whereas the more pronounced late phase required the presence of live virus and infection of the epithelium. Partial (< 50%) cytopathic effects were noted at 48 h and progressed to 75% at 96 h. The monolayer was still intact at 96 h. Inhibitors of nitric oxide, including NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME), and aminoguanidine had no effect on IL-8 release or IL-8 mRNA induction. We did, however, demonstrate a dose-dependent decrease in IL-8 release and IL-8 mRNA induction in RSV-infected epithelial treated with the antioxidants dimethyl sulfoxide (DMSO) or 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Peak effects were noted at a concentration of 2% DMSO and 50 microM DMPO. The antioxidants did not inhibit viral replication or infection. This data suggest that RSV-induced IL-8 production in airway epithelium is mediated via changes in oxidant tone. The data also suggest a potential therapeutic role for antioxidants in RSV infections.

Publication types

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

MeSH terms

  • Antioxidants / pharmacology
  • Blotting, Northern
  • Epithelium / metabolism
  • Epithelium / virology
  • Humans
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Laryngeal Neoplasms / virology
  • Nitric Oxide / antagonists & inhibitors
  • Oxidants / metabolism*
  • RNA, Messenger / biosynthesis
  • Respiratory Syncytial Virus Infections / metabolism*
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / virology
  • Virus Replication / drug effects
  • Virus Replication / physiology


  • Antioxidants
  • Interleukin-8
  • Oxidants
  • RNA, Messenger
  • Nitric Oxide