Circulating mitochondrial<i>N</i>-formyl peptides contribute to secondary nosocomial infection in patients with septic shock

Abstract

Significance Septic shock commonly leads to multiorgan injury both directly via tissue inflammation and secondarily via hypoperfusion, but both can result in mitochondrial N -formyl peptide (mtFP) release into the circulation. However, no studies have evaluated the role of circulating mtFPs during septic shock. We found that a relatively high plasma nicotinamide adenine dinucleotide dehydrogenase subunit-6 (the most potent human mtFP) level was independently associated with the development of secondary infection in patients with septic shock and that the increased susceptibility to secondary infection is partly attributed to the suppression of polymorphonuclear leukocyte (PMN) chemotaxis by mtFP occupancy of formyl peptide receptor-1. Incorporation of these findings into therapeutic strategies may improve clinical outcomes in septic shock patients by preventing PMN chemotactic anergy.