Kinins Are Generated in Nasal Secretions during Influenza A Infections in Ferrets

Abstract

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.

Protective activity of ketoprofen lysine salt against the pulmonary effects induced by bradykinin in guinea-pigs

“…Among several proinflammatory agents, BK has been implicated as an important mediator of both bronchoconstriction and airway oedema formation [4,5]. In addition, several pieces of evidence support a role for BK and related kinins in the pathogenesis of inflammatory disease in the upper airways associated with viral infections [7,8]. Therefore, we have investigated the effect of the well-known nonsteroidal ant• drug KLS on the pathological events triggered within the guinea-pig respiratory system by BK and by another inflammatory autacoid LTC4.…”

“…Nevertheless, the other non-steroidal ant• drug flurbiprofen, has been demonstrated to be effective in reducing oedema associated with upper airway inflammation [27], while ibuprofen has been shown to ameliorate inflammatory symptoms associated with tonsillitis and pharyngitis in children [28]. Therefore, since BK and to some extent LTC 4 represent important mediators of the inflammatory processes associated with different airway diseases, including allergic rhinitis, common colds, asthma and bronchitis [5,6,7,8,10], data obtained in the present study strongly support a role for KLS also in the therapy of such respiratory diseases.…”

“…Several studies have also provided evidence for a role of BK in respiratory tract diseases, including asthma, chronic bronchitis and inflammatory disorders of the upper airways, such as allergic rhinitis and viral infections [4,5]. Indeed, BK and other kinins are generated in nasal secretion during allergen challenge of allergic individuals, and are the only mediators detected in nasal secretion during natural rhinovirus colds in humans or influenza A virus infection in ferrets [6][7][8], their production in these inflammatory reactions correlating with the appearance of symptoms. The inflammatory properties of BK further support its involvement in the inflammatory responses in the airways.…”

Double-stranded RNA increases kinin B1 receptor expression and function in human airway epithelial cells

“…Animal models also suggest a participatory role for kinin generation during respiratory viral infections. Objective signs of respiratory disease in ferrets inoculated with influenza virus corresponded with the appearance of kinins in the nasal lavages, and airway hyper-responsiveness following parainfluenza-3 infection in guinea pig correlated with the generation of bradykinin [10,11].…”

Upper airway viral infections

“…Moreover, while older antihistamines that display anticholinergic and sedative properties do reduce rhinorrhea during colds, second generation antihistamines lacking these side effects are ineffective [54]. By contrast, other mediators, such as kinins and leukotrienes have been associated with infections due to more than one type of common respiratory virus [22,[55][56][57]. Defining the role of each of these mediators in disease pathogenesis will, again, require studies with effective and selective antagonists.…”