PT  - JOURNAL ARTICLE
AU  - Declan Byrnes
AU  - Claire Masterson
AU  - Shahd Horie
AU  - Jack Brady
AU  - Hector Gonzalez
AU  - Sean Mccarthy
AU  - Daniel O'Toole
AU  - John Laffey
TI  - Therapeutic potential of mesenchymal stem cells to attenuate immune cell tolerance in a late stage model of sepsis
AID  - 10.1183/13993003.congress-2020.2579
DP  - 2020 Sep 07
TA  - European Respiratory Journal
PG  - 2579
VI  - 56
IP  - suppl 64
4099  - http://erj.ersjournals.com/content/56/suppl_64/2579.short
4100  - http://erj.ersjournals.com/content/56/suppl_64/2579.full
SO  - Eur Respir J2020 Sep 07; 56
AB  - Introduction: Patients who survive early stage sepsis may progress to late stage sepsis which is characterised by immunosuppression believed to be due, in part, to immune cell paralysis. We have previously shown that Mesenchymal Stem Cells (MSCs) are effective in preclinical models of early stage sepsis (Devaney et al., 2015) and to restore macrophage function in early clinical sepsis. We sought to develop in vivo and in vitro late stage sepsis models to assess if MSCs could restore immune cell homeostasis in this setting.Methods: We established an in vivo model of pulmonary sepsis by intratracheal administration of K.pneumoniae to Sprague-Dawley rats. MSCs were administered at day two and immune cell and cytokine secretion profiles in the Bronchoalveolar Lavage (BAL) and blood were analysed at day five. An in vitro endotoxin tolerance model was then established using immune cell lines and primary macrophages from blood and BAL exposed to repeated high levels of endotoxin.Results: MSCs improve paralysed immune cell responsiveness to an endotoxin stimulus ex vivo as demonstrated by a restoration of cytokine secretion in cells isolated from treated animal models (Figure 1). Conclusions: MSCs have the potential to reverse late sepsis induced immune cell dysfunction caused by prolonged exposure to bacterial endotoxin ex vivo.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 2579.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).