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

Thomas Rimmelé, Ata M. 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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numberR59
JournalCritical Care
Volume17
Issue number2
DOIs
StatePublished - Mar 26 2013

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Cellular Immunity
Sepsis
Leukocytes
Cytokines
Interleukin-8
Cell Communication
Equipment and Supplies
Monocytes
Neutrophils
Therapeutics
Septic Shock
Immunity
Healthy Volunteers
Polymers
Up-Regulation
Research Personnel
Lymphocytes
Inflammation
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

Rimmelé, T., Kaynar, A. M., McLaughlin, J. N., Bishop, J. V., Fedorchak, M. V., Chuasuwan, A., ... Kellum, J. A. (2013). Leukocyte capture and modulation of cell-mediated immunity during human sepsis: An ex vivo study. Critical Care, 17(2), [R59]. https://doi.org/10.1186/cc12587
Rimmelé, Thomas ; Kaynar, Ata M. ; McLaughlin, Joseph N. ; Bishop, Jeffery V. ; Fedorchak, Morgan V. ; Chuasuwan, Anan ; Peng, Zhiyong ; Singbartl, Kai ; Frederick, Daniel R. ; Zhu, Lin ; Carter, Melinda ; Federspiel, William J. ; Zeevi, Adriana ; Kellum, John A. / Leukocyte capture and modulation of cell-mediated immunity during human sepsis : An ex vivo study. In: Critical Care. 2013 ; Vol. 17, No. 2.
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abstract = "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.",
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Rimmelé, T, Kaynar, AM, McLaughlin, JN, Bishop, JV, Fedorchak, MV, Chuasuwan, A, Peng, Z, Singbartl, K, Frederick, DR, Zhu, L, Carter, M, Federspiel, WJ, Zeevi, A & Kellum, JA 2013, 'Leukocyte capture and modulation of cell-mediated immunity during human sepsis: An ex vivo study', Critical Care, vol. 17, no. 2, R59. https://doi.org/10.1186/cc12587

Leukocyte capture and modulation of cell-mediated immunity during human sepsis : An ex vivo study. / Rimmelé, Thomas; Kaynar, Ata M.; McLaughlin, Joseph N.; Bishop, Jeffery V.; Fedorchak, Morgan V.; Chuasuwan, Anan; Peng, Zhiyong; Singbartl, Kai; Frederick, Daniel R.; Zhu, Lin; Carter, Melinda; Federspiel, William J.; Zeevi, Adriana; Kellum, John A.

In: Critical Care, Vol. 17, No. 2, R59, 26.03.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Leukocyte capture and modulation of cell-mediated immunity during human sepsis

T2 - An ex vivo study

AU - Rimmelé, Thomas

AU - Kaynar, Ata M.

AU - McLaughlin, Joseph N.

AU - Bishop, Jeffery V.

AU - Fedorchak, Morgan V.

AU - Chuasuwan, Anan

AU - Peng, Zhiyong

AU - Singbartl, Kai

AU - Frederick, Daniel R.

AU - Zhu, Lin

AU - Carter, Melinda

AU - Federspiel, William J.

AU - Zeevi, Adriana

AU - Kellum, John A.

PY - 2013/3/26

Y1 - 2013/3/26

N2 - 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.

AB - 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.

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Rimmelé T, Kaynar AM, McLaughlin JN, Bishop JV, Fedorchak MV, Chuasuwan A et al. Leukocyte capture and modulation of cell-mediated immunity during human sepsis: An ex vivo study. Critical Care. 2013 Mar 26;17(2). R59. https://doi.org/10.1186/cc12587