Pseudomonas aeruginosa is a frequent cause of lung
infections, particularly in
chronic infections in
cystic fibrosis patients. However, treatment is challenging due to P. aeruginosa evasion of the host immune system and the rise of
antibiotic resistant strains.
Host defense peptides (HDPs) and synthetic derivatives called innate defense regulators (IDRs) have shown promise in several
infection models as an alternative to
antibiotic treatment. Here we tested
peptide IDR-1002 against P. aeruginosa in vitro and in vivo. Treatment of bronchial epithelial cells and macrophages with
IDR-1002 or in combination with live P. aeruginosa or its LPS led to the reduction of agonist-induced
cytokines and
chemokines and limited cell killing by live P. aeruginosa. In an in vivo model using P. aeruginosa combined with
alginate to mimic a chronic model,
IDR-1002 did not reduce the bacterial burden in the lungs, but
IDR-1002 mice showed a significant decrease in
IL-6 in the lungs and in gross pathology of
infection, while histology revealed that
IDR-1002 treated mice had reduced alveolar macrophage infiltration around the site of
infection and reduced
inflammation. Overall, these results indicate that
IDR-1002 has promise for combating P. aeruginosa lung
infections and their resulting
inflammation.