TY - JOUR
T1 - Attenuation of virus-induced airway dysfunction in rats treated with imiquimod
AU - Stokes, J. R.
AU - Sorkness, R. L.
AU - Kaplan, M. R.
AU - Castleman, W. L.
AU - Tomai, M. A.
AU - Miller, R. L.
AU - Lemanske, R. F.
PY - 1998/2
Y1 - 1998/2
N2 - 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.
AB - 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.
KW - Asthma
KW - Cytokines
KW - Interferon-α
KW - Parainfluenza
KW - Rats
KW - Sendai virus
UR - http://www.scopus.com/inward/record.url?scp=0031910959&partnerID=8YFLogxK
U2 - 10.1183/09031936.98.11020324
DO - 10.1183/09031936.98.11020324
M3 - Article
C2 - 9551732
AN - SCOPUS:0031910959
SN - 0903-1936
VL - 11
SP - 324
EP - 329
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 2
ER -