Host defence peptides (HDPs) are small peptides with antibacterial and immunomodulatory properties that represent a novel approach to anti-infective therapy. Innate defence regulator (IDR) peptides, such as IDR-1018, are synthetic variants of HDPs that are more potent and less toxic than their naturally-occurring counterparts. IDR-1018 kills bacteria, exhibits potent chemokine activities, and decreases LPS-induced TNF-α release. The goal of the current study was to determine whether IDR-1018 protects mice in the Pseudomonas aeruginosa acute lung infection model. To this end, CD1 mice were given IDR-1018 (4 mg/kg) or the saline control intravenously 4 h prior to infection. Mice were infected intranasally with P. aeruginosa (1 x 10^6). Mice were sacrificed 18 h post infection, and blood and bronchoalveolar lavage fluid (BALF) was collected. P. aeruginosa CFUs and leukocyte counts in the BALF were determined. Cytokine concentrations (TNF-α, MCP-1, KC, and IL-6) in the blood and BALF were quantified by ELISA. Our data showed that IDR-1018-treated mice had fewer CFUs and neutrophils and more monocytes in the BALF, and lower concentrations of proinflammatory cytokines in the BALF and in the blood than did saline-treated mice. These results suggest that IDR-1018 may have potential for the treatment of acute lung infections. Future studies aim to optimize the delivery strategy by identifying a delivery vehicle that enhances the half life and ease of peptide delivery.
- Copyright © 2013 by The American Association of Immunologists, Inc.