Extracorporeal cytokine adsorption reduces systemic cytokine storm and improves graft function in lung transplantation

Jonas Peter Ehrsam; Stephan Arni; Miriam Weisskopf; Miriam Nowack; Ilhan Inci

doi:10.1016/j.xjon.2023.06.011

Extracorporeal cytokine adsorption reduces systemic cytokine storm and improves graft function in lung transplantation

JTCVS Open. 2023 Jul 4:15:497-507. doi: 10.1016/j.xjon.2023.06.011. eCollection 2023 Sep.

Authors

Jonas Peter Ehrsam^{1

2}, Stephan Arni³, Miriam Weisskopf⁴, Miriam Nowack⁵, Ilhan Inci^{1

2}

Affiliations

¹ School of Medicine, University of Zurich, Zurich, Switzerland.
² Klinik Hirslanden Zurich, Thoracic Surgery Clinic, Zurich, Switzerland.
³ Center for Surgical Research, University Hospital Zurich, Zurich, Switzerland.
⁴ Center for Preclinical Development, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁵ Department of Pathology, University Hospital Zurich, Zurich, Switzerland.

Abstract

Objectives: Ischemia-reperfusion injury often coincides with a cytokine storm, which can result in primary graft dysfunction following lung transplantation. Our previous research has demonstrated allograft improvement by cytokine adsorption during ex vivo lung perfusion. The aim of this study was to investigate the effect of in vivo extracorporeal cytokine adsorption in a large animal model.

Materials and methods: Pig left lung transplantation was performed following 24 hours of cold ischemic storage. Observation period after transplantation was 24 hours. In the treatment group (n = 6), extracorporeal CytoSorb adsorption was started 30 minutes before reperfusion and continued for 6 hours. A control group (n = 3) did not receive adsorber treatment.

Results: During adsorption, we consistently noticed a significant decrease in plasma proinflammatory interleukin (IL)-2, trends of less proinflammatory, tumor necrosis factor- α, IL-1α, and granulocyte-macrophage colony-stimulating factor as well as significantly reduced systemic neutrophils. In addition, a significantly lower peak airway pressure was detected during the 6 hours of adsorption. After 24 hours of observation, when evaluating the left lung allograft independently, we observed significantly improved CO2 removal, partial pressure of oxygen/inspired oxygen fraction ratio, and less acidosis in the treatment group. At autopsy, bronchoalveolar lavage results exhibited significantly lower recruitment of cells and less pro-inflammatory IL-1α, IL-1β, IL-6, and IL-8 in the treatment group. Histologically, the treatment group had a strong trend, indicating less neutrophil invasion into the alveolar space.

Conclusions: Based on our findings, cytokine adsorption during and after reperfusion is a viable approach to reducing posttransplant inflammation following lung transplantation. CytoSorb may increase the acceptance of extended criteria donor lungs, which are more susceptible to ischemia-reperfusion injury.

Keywords: CytoSorb; extracorporeal cytokine adsorption; ischemia–reperfusion injury; lung transplantation.