Purpose: To investigate the effect of bryostatin 1 on respiratory syncytial virus (RSV) infection in vitro in lung alveolar cells and in vivo in a mice model.
Methods: RSV infection in the mice was induced by the administration of 2 x 106 PFU viral particles intranasally in the left nostril. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used for the determination of changes in interleukin expression.
Results: Bryostatin 1 treatment of RSV-infected BEAS-2B cells significantly (p < 0.05) inhibited viability. The mortality of mice infected with RSV markedly decreased on treatment with bryostatin 1. The pulmonary damage induced by RSV infection was also prevented in mice treated with bryostatin 1. Treatment of the RSV infected mice with bryostatin 1 caused a dose-based suppression of IL 1β/ 18 and TNF α generation (p < 0.05). Bryostatin 1 pre-treatment at doses 2, 6 and 12 mg/kg led to reduction of NLRP3, ASC and caspase 1 proteins, as well as a significant decrease in the expression of mRNA corresponding to NLRP3, ASC and caspase 1 (p< 0.05).
Conclusion: The results demonstrate that bryostatin 1 treatment of RSV-infected BEAS-2B cells prevents reduction in its viability. Moreover, pre-treatment of RSV-infected mice with bryostatin 1 improves mortality and prevents pulmonary tissue damage by down-regulating NLRP3 activation. Therefore, bryostatin 1 may be an option for the development of an effective treatment for pneumoni