Attenuation of virus-induced airway dysfunction in rats treated with imiquimod

J. R. Stokes, R. L. Sorkness, M. R. Kaplan, W. L. Castleman, M. A. Tomai, R. L. Miller, R. F. Lemanske

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Viral respiratory infections cause acute airway abnormalities consisting of inflammation and physiological dysfunction in both animals and humans. It is likely that inflammatory cell products, such as cytokines, contribute substantially to viral-induced airway dysfunction. We hypothesized that imiquimod, an immune response enhancing agent that induces interferon-α, would attenuate the development of airway dysfunction during acute viral illness in rats. Adult Brown Norway rats were inoculated with parainfluenza type 1 (Sendai) virus or sterile vehicle, and treated with either imiquimod or water. Respiratory system resistance (Rrs), arterial oxygen tension (Pa,O2), lung viral titres and bronchoalveolar lavage (BAL) leucocyte counts were measured in anaesthetized, paralysed, ventilated rats. Virus-infected, water-treated rats had a significant decrease in Pa,O2 and had significant increases in leucocyte count and Rrs when compared to both the virus-infected, imiquimod-treated, (Pa,O2, p = 0.03; leucocyte count, p = 0.02; and Rrs p = 0.009) and noninfected, water-treated rats (Pa,O2, p = 0.007; leucocyte count, p = 0.001; and Rrs, p = 0.01). In addition, imiquimod suppressed BAL eosinophils in both virus-infected (p = 0.02) and noninfected (p = 0.001) groups, and lowered overall virus titres (p = 0.03). Thus, both virus-induced airway inflammation and physiological dysfunction were attenuated significantly by imiquimod treatment in this animal model. By further delineating mechanisms by which infections induce airway dysfunction in animal models, more specific pharmacological interventions can be developed for the treatment of virus-induced asthma.

Original languageEnglish
Pages (from-to)324-329
Number of pages6
JournalEuropean Respiratory Journal
Volume11
Issue number2
DOIs
StatePublished - Feb 1998

Keywords

  • Asthma
  • Cytokines
  • Interferon-α
  • Parainfluenza
  • Rats
  • Sendai virus

Fingerprint

Dive into the research topics of 'Attenuation of virus-induced airway dysfunction in rats treated with imiquimod'. Together they form a unique fingerprint.

Cite this