Leukocyte capture and modulation of cell-mediated immunity during human sepsis: an ex vivo study |
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Authors: | Thomas Rimmelé Ata Murat Kaynar Joseph N McLaughlin Jeffery V Bishop Morgan V Fedorchak Anan Chuasuwan Zhiyong Peng Kai Singbartl Daniel R Frederick Lin Zhu Melinda Carter William J Federspiel Adriana Zeevi John A Kellum |
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Institution: | 1.The CRISMA (Clinical Research, Investigation, and Systems Modeling of Acute Illness) Center, Department of Critical Care Medicine, University of Pittsburgh, School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA;2.McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA 15219, USA;3.The Thomas E. Starzl Transplantation Institute, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15261, USA |
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Abstract: | IntroductionPromising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. However, the mechanisms by which these therapies exert beneficial effects remain unclear. Some investigators have suggested that removal of activated leukocytes from the circulation might help ameliorate remote organ injury. We designed an extracorporeal hemoadsorption device capable of capturing both cytokines and leukocytes in order to test the hypothesis that leukocyte capture would alter circulating cytokine profiles and influence immunological cell-cell interactions in whole blood taken from patients with sepsis.MethodsWe performed a series of ex vivo studies in 21 patients with septic shock and 12 healthy volunteers. Blood circulated for four hours in closed loops with four specially designed miniaturized extracorporeal blood purification devices including two different hemoadsorption devices and a hemofilter in order to characterize leukocyte capture and to assess the effects of leukocyte removal on inflammation and immune function.ResultsHemoadsorption was selective for removal of activated neutrophils and monocytes. Capture of these cells led to local release of certain cytokines, especially IL-8, and resulted in complex cell-cell interactions involved in cell-mediated immunity. Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function.ConclusionsMonocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity. Further studies are needed to understand better these cellular interactions in order to help design better blood purification therapies. |
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