Inhibition of Phosphodiesterase-4 during Pneumococcal Pneumonia Reduces Inflammation and Lung Injury in Mice

• DOI: 10.1165/rcmb.2015-0083oc
• Publication Date: 2015-12-17T22:10:15Z
• Authors: Luciana P. Tavares; Cristiana C. Garcia; Juliana P. Vago; Celso M. Queiroz-...; Izabela Galvão; Bruna A. David; Milene A. Rachid; Patrícia M. R. Silva; Remo C. Russo; Mauro M. Teixeira; Lirlândia P. Sousa
• Keywords: Pneumococcal pneumonia

Pneumococcal pneumonia is a leading cause of mortality worldwide. The inflammatory response to bacteria necessary control infection, but it may also contribute tissue damage. Phosphodiesterase-4 inhibitors, such as rolipram (ROL), effectively reduce inflammation. Here, we examined the impact ROL in pneumococcal murine model. Mice were infected intranasally with 10(5)-10(6) CFU Streptococcus pneumoniae, treated prophylactic or therapeutic schedule combination, not, antibiotic ceftriaxone. Inflammation and counts assessed, ex vivo phagocytosis assays performed. treatment during S. pneumoniae infection decreased neutrophil recruitment into lungs airways reduced lung injury. Prophylactic cytokine levels airways. Although modulation inflammation by ameliorated pneumonia, burden was not reduced. On other hand, therapy without reducing infiltration, level, Combined ceftriaxone lethality rates more efficient inflammation, increasing proresolving protein annexin A1 (AnxA1) expression, bacterial enhancing phagocytosis. Lack AnxA1 increased induced infection. These data show that immunomodulatory effects phosphodiesterase-4 inhibitors are useful severe suggest their potential benefit adjunctive infectious diseases.