ATTENUATION OF VIRUS-INDUCED AIRWAY DYSFUNCTION IN RATS TREATED WITH IMIQUIMOD

Viral respiratory infections cause acute airway abnormalities consisti ng of inflammation and physiological dysfunction in both animals and h umans, It is likely that inflammatory cell products, such as cytokines , contribute substantially to viral-induced airway dysfunction. We hyp othesized that imiquimod, an immune response enhancing agent that indu ces interferon-alpha, would attenuate the development of airway dysfun ction during acute viral illness in rats. Adult Brown Norway rats were inoculated with parainfluenza type 1 (Sendai) virus or sterile vehicl e, and treated with either imiquimod or water. Respiratory system resi stance (Rrs), arterial oxygen tension (Pa,O-2), lung viral titres and bronchoalveolar lavage (BAL) leucocyte counts were measured in anaesth etized, paralysed, ventilated rats. Virus-infected, water-treated rats had a significant decrease in Pa,O-2 and had significant increases in leucocyte count and Rrs when compared to both the virus-infected, imi quimod-treated, (Pa,O-2, p=0.03; leucocyte count, p=0.02; and Rrs, p=0 .009) and noninfected, water-treated rats (Pa,O-2, p=0.007; leucocyte count, p=0.001; and Rrs, p=0.01). In addition, imiquimod suppressed BA L 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 attenua ted significantly by imiquimod treatment in this animal model, By furt her delineating mechanisms by which infections induce airway dysfuncti on in animal models, more specific pharmacological interventions can b e developed for the treatment of virus-induced asthma.