Ablation of PDE4A Exacerbates Pseudomonas aeruginosa-Induced Acute Lung Injury in Mice.

Ablation of PDE4A produces detrimental effects in this model of acute PA-lung infection. Current studies aim to determine whether an impaired bacterial killing, and the resulting increase in bacterial load, are responsible for the hyperinflammation, or whether these are independent effects of PDE4A ablation. PAN-PDE4 inhibition mimics some of the beneficial effects of selective PDE4B ablation, but also some of the detrimental effects of PDE4A ablation. These findings suggest that selective inactivation of PDE4B may be a more effective therapeutic approach, compared to PAN-PDE4 inhibition, in settings of acute PA-lung infection.