Infection of ferrets with influenza A virus results in a disease syndrome that is similar to that observed in humans. To examine the pathophysiology of this disease, ferrets were challenged with either H1N1 influenza virus or placebo. Sign scores and rectal temperatures were recorded periodically during the 9 days after infection. Nasal lavages were also collected during this time period and the content of kinins, histamine, cells, and total protein in these lavages was assessed. In infected animals (n = 17) compared to healthy controls (n = 14), sign scores were first significantly elevated at 30 h postinfection. Sign scores peaked at 48 to 72 h postinfection and then slowly declined, although they remained significantly elevated up to 168 h postinfection. Kinin levels were significantly correlated with signs. Associated with increased sign scores and kinins, elevations were observed in the levels of total protein and cells in nasal lavages of infected animals. In contrast to the increases in kinin levels that were observed during influenza infections, histamine concentrations in nasal lavages did not change in response to infection. We conclude that kinins are generated in nasal secretions during influenza A infections and that these potent vasoactive peptides may contribute to the symptomatology of such infections. The study of influenza infections in ferrets provides a convenient animal model in which to evaluate further the role of kinins in the pathogenesis of upper respiratory tract infections.

Alterations induced in the upper airways of ferrets by intranasal provocation with methacholine (MC) and histamine (HS) were monitored using proton magnetic resonance imaging (MRI) and spin-spin relaxation rate (R2) measurements. Both MC and HS cause a significant increase in the MRI signal intensity and a decrease in R2 in the nasal turbinates. A dose-dependent response is observed for 20 to 315 nmol of HS, with a maximum increase in intensity of ca. 50% occurring above 80 nmol. A single unilateral challenge with MC yields a 62 +/- 3% increase in intensity. Control animals (saline-treated) show little change in image intensity. MC and HS cause decreases in the proton R2 by -27.0 +/- 5.5% and -17.2 +/- 4.3%, respectively. These data are indicative of an accumulation of fluid in the nasal airways. MRI provides an effective means to monitor changes in the nasal airways which occur as a result of pharmacological treatment.