Decreased LPS-induced lung injury in pigs treated with a lung surfactant protein A-derived nonapeptide that inhibits peroxiredoxin 6 activity

This study addressed the efficacy of a liposome-encapsulated 9 amino acid peptide (PIP-2) for the prevention or treatment of acute lung injury (ALI) +/- sepsis. PIP-2 inhibits the PLA2 activity of peroxiredoxin 6, thereby preventing Rac release and activation of NADPH oxidases, types 1 and 2. Female Yorkshire pigs were infused intravenously with lipopolysaccharide (LPS) + liposomes (untreated) or LPS + PIP-2 encapsulated in liposomes (treated). Pigs were mechanically ventilated and continuously monitored; they were euthanized after 8 hours or earlier if pre-established humane endpoints were reached. Control pigs (mechanical ventilation, no LPS) were essentially unchanged over the 8-hour study. LPS administration resulted in systemic inflammation with manifestations of clinical sepsis, decreased lung compliance, and a marked decrease in the arterial PO2 with vascular instability leading to early euthanasia of 50% of untreated animals. PIP-2 treatment significantly reduced the requirement for supportive vasopressors and the manifestations of lung injury so that only 25% of animals required early euthanasia. Broncho-alveolar lavage fluid from PIP-2- treated versus untreated pigs showed markedly lower total protein, cytokines (TNF-α, IL-6, IL-1β), and myeloperoxidase levels. Thus, the porcine LPS-induced sepsis model was associated with moderate to severe lung pathophysiology compatible with ALI while treatment with PIP-2 markedly decreased lung injury, cardiovascular instabili...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Source Type: research