Synthetic host defense peptide IDR-1002 reduces inflammation in Pseudomonas aeruginosa lung infection

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.