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Leukocyte capture and modulation of cell-mediated immunity during human sepsis: An ex vivo study

Rimmelé, T and Kaynar, AM and McLaughlin, JN and Bishop, JV and Fedorchak, MV and Chuasuwan, A and Peng, Z and Singbartl, K and Frederick, DR and Zhu, L and Carter, M and Federspiel, WJ and Zeevi, A and Kellum, JA (2013) Leukocyte capture and modulation of cell-mediated immunity during human sepsis: An ex vivo study. Critical Care, 17 (2). ISSN 1364-8535

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Introduction: Promising 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.Methods: We 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. Results: Hemoadsorption 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 cellmediated immunity. Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function. Conclusions: Monocyte 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. © 2013 Rimmelé et al.; licensee BioMed Central Ltd.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Rimmelé, T
Kaynar, AMkaynar@pitt.eduAMK960000-0001-8847-0450
McLaughlin, JN
Bishop, JV
Fedorchak, MVmorgandileo@pitt.eduMOD8
Chuasuwan, A
Peng, Z
Singbartl, K
Frederick, DR
Zhu, L
Carter, MMelinda.Berkey@pitt.eduMJC2
Federspiel, WJfederspielwj@pitt.eduWFEDERSP0000-0002-7068-6779
Zeevi, Azeevi@pitt.eduZEEVI
Kellum, JAkellum@pitt.eduKELLUM0000-0003-1995-2653
Centers: Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 26 March 2013
Date Type: Publication
Journal or Publication Title: Critical Care
Volume: 17
Number: 2
DOI or Unique Handle: 10.1186/cc12587
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: Yes
ISSN: 1364-8535
Date Deposited: 07 Oct 2016 15:15
Last Modified: 17 Sep 2021 12:01


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