Distribution of immunoreactive endothelin in the lungs of mice during respiratory viral infection.

Respiratory tract viral infections are associated with the generation of a wide array of pro-inflammatory cytokines, some of which enhance the release of the potent airway smooth muscle spasmogen, endothelin, from respiratory epithelial cells in tissue culture. The aim of this study was to determine whether the content and distribution of immunoreactive endothelin in the intact murine lung is increased during the course of a respiratory tract viral infection. Mice were inoculated intranasally with Influenza A/PR-8/34 virus or sterile vehicle and at various days postinoculation were sacrificed, and their lungs processed for either fluorescence immunohistochemistry with rabbit anti-endothelin sera or measurement of immunoreactive endothelin with an enzyme-linked immunosorbent assay (ELISA). At 2 and 4 days postinoculation, the content of immunoreactive endothelin in lung extracts of virus-infected mice was approximately twice that present in lung extracts from control mice (n=3-4, p<0.05). Consistent with this, an increased intensity and broader distribution of fluorescent immunohistochemical staining for endothelin was observed in the airway epithelium of the trachea and intrapulmonary airways of virus-infected mice. This study has clearly demonstrated that respiratory tract viral infection is associated with an increased content and broader distribution of immunoreactive endothelin within the lungs of mice. Whether the elevated content of endothelin contributes to the symptoms of virus-induced hyperresponsiveness or to virus-induced exacerbations of asthma remains to be established.