Intrabronchial Application of Extracellular Histones Shows No Proinflammatory Effects in Swine in a Translational Pilot Study

Abstract

Objective: Extracellular histones have been identified as one molecular factor that can cause and sustain alveolar damage and were linked to high mortality rates in critically ill patients. In this pilot study, we wanted to validate the proinflammatory in vivo effects of local and systemic histone application in a prospective translational porcine model. This was combined with the evaluation of an experimental acute lung injury model using intrabronchial lipopolysaccharides, which has been published previously.Results: The targeted application of histones was successful in all animals. Animals showed decreased oxygenation after instillation, but no differences could be detected between the sham and histone treatments. Additionally, intravenous histone injection had no effect. The histologic analyses and inflammatory responses indicated that there were no differences in tissue damage between the groups.