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

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 - Crit Care (2013)

Bottom Line: However, the mechanisms by which these therapies exert beneficial effects remain unclear.Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function.Monocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity.

View Article: PubMed Central - HTML - PubMed

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 cell-mediated 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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Related in: MedlinePlus

The four ex vivo miniaturized extracorporeal circuits (hemofiltration, hemadsorption with large beads, hemoadsorption with small beads and sham). Blood was circulated through these closed circuits for four hours. HA-LB, hemoadsorption with large beads; HA-SB, hemoadsorption with small beads; HF, hemofiltration; P, mini-pump; RF, replacement fluid; UF, ultrafiltrate.
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Figure 1: The four ex vivo miniaturized extracorporeal circuits (hemofiltration, hemadsorption with large beads, hemoadsorption with small beads and sham). Blood was circulated through these closed circuits for four hours. HA-LB, hemoadsorption with large beads; HA-SB, hemoadsorption with small beads; HF, hemofiltration; P, mini-pump; RF, replacement fluid; UF, ultrafiltrate.

Mentions: Blood was collected into standard vacuum-collection tubes. The experiments consisted of perfusing blood through four different closed miniaturized ex vivo extracorporeal circuits over a period of four hours: 1) a hemoadsorption device containing 1.5 g of large (approximately 550 to 600 μm diameter) polystyrene divinylbenzene copolymer beads (Cytosorb™; CytoSorbents Corporation, Monmouth Junction, NJ, USA); 2) a hemoadsorption circuit containing 2.5 g of small (70 to 75 μm diameter) Cytosorb beads; 3) a hemofiltration circuit with a mini hemofiltration device (Oxiris®, Gambro-Hospal, Meyzieu, France); and 4) a sham circuit consisting of the extracorporeal circuit with no blood purification device (that is, a tubing circuit with just an empty cartridge) (Figure 1).


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

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 - Crit Care (2013)

The four ex vivo miniaturized extracorporeal circuits (hemofiltration, hemadsorption with large beads, hemoadsorption with small beads and sham). Blood was circulated through these closed circuits for four hours. HA-LB, hemoadsorption with large beads; HA-SB, hemoadsorption with small beads; HF, hemofiltration; P, mini-pump; RF, replacement fluid; UF, ultrafiltrate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672497&req=5

Figure 1: The four ex vivo miniaturized extracorporeal circuits (hemofiltration, hemadsorption with large beads, hemoadsorption with small beads and sham). Blood was circulated through these closed circuits for four hours. HA-LB, hemoadsorption with large beads; HA-SB, hemoadsorption with small beads; HF, hemofiltration; P, mini-pump; RF, replacement fluid; UF, ultrafiltrate.
Mentions: Blood was collected into standard vacuum-collection tubes. The experiments consisted of perfusing blood through four different closed miniaturized ex vivo extracorporeal circuits over a period of four hours: 1) a hemoadsorption device containing 1.5 g of large (approximately 550 to 600 μm diameter) polystyrene divinylbenzene copolymer beads (Cytosorb™; CytoSorbents Corporation, Monmouth Junction, NJ, USA); 2) a hemoadsorption circuit containing 2.5 g of small (70 to 75 μm diameter) Cytosorb beads; 3) a hemofiltration circuit with a mini hemofiltration device (Oxiris®, Gambro-Hospal, Meyzieu, France); and 4) a sham circuit consisting of the extracorporeal circuit with no blood purification device (that is, a tubing circuit with just an empty cartridge) (Figure 1).

Bottom Line: However, the mechanisms by which these therapies exert beneficial effects remain unclear.Inhibition of cell adherence reversed the cytokine release and the effects on lymphocyte function.Monocyte and neutrophil capture using a sorbent polymer results in upregulation of IL-8 and modulation of cell-mediated immunity.

View Article: PubMed Central - HTML - PubMed

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 cell-mediated 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.

Show MeSH
Related in: MedlinePlus