Effects of 4-ipomeanol on bovine parainfluenza type 3 virus-induced pneumonia in calves.

Previous research has demonstrated that 4-ipomeanol toxicosis can enhance the severity of para-influenza virus-induced pneumonia in mice. The objectives of this study were to determine whether calves are susceptible to 4-ipomeanol-induced enhancement of parainfluenza type 3 viral pneumonia and to determine whether 4-ipomeanol alters pulmonary replication of parainfluenza virus. Male Holstein calves were injected with either 4-ipomeanol (3 mg/kg) or vehicle (polyethylene glycol) 3 days prior to intratracheal inoculation with either parainfluenza virus or sham inoculum of culture medium. Calves in the four treatment groups (ipomeanol-parainfluenza, ipomeanol-medium, vehicle-parainfluenza, and vehicle-medium) were necropsied at 5 days after inoculation with parainfluenza virus or medium. The lungs were studied by correlated methods of light and electron microscopy, digitizing morphometry and pulmonary lavage to quantitate the severity of pneumonia. Pulmonary viral titers were determined, and viral antigen was identified in the lung by immunoperoxidase technique. The calves in the ipomeanol-virus treatment group had over a 9-fold higher (P less than 0.05) volume density of virus-induced interstitial pneumonia than did the calves in the other three treatment groups. This 4-ipomeanol-enhanced viral pneumonia was associated with significantly greater (P less than 0.05) numbers of pulmonary macrophages and neutrophils in the lavage fluid and higher (P less than 0.05) pulmonary titers of pulmonary infectious parainfluenza virus. Four-ipomeanol-enhanced viral pneumonia was characterized in part by extensive hyperplasia of type II alveolar epithelial cells and by dense aggregates of macrophages and neutrophils in alveolar spaces and interalveolar septa. The results indicate that 4-ipomeanol exacerbates interstitial pneumonia in calves induced by bovine parainfluenza type 3 virus.