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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

Effects of extracorporeal circuits on white blood cells (WBC), neutrophils (PMN), monocytes (Mono), lymphocytes (Lymph) and platelets (Plts). Results are expressed as % of cells present before circulation through the circuits (uncirculated condition), in blood obtained from septic patients and healthy volunteers (medians with interquartile ranges). *P < .05, **P < .01, ***P < .001 compared with Sham.
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Figure 2: Effects of extracorporeal circuits on white blood cells (WBC), neutrophils (PMN), monocytes (Mono), lymphocytes (Lymph) and platelets (Plts). Results are expressed as % of cells present before circulation through the circuits (uncirculated condition), in blood obtained from septic patients and healthy volunteers (medians with interquartile ranges). *P < .05, **P < .01, ***P < .001 compared with Sham.

Mentions: Blood circulation through all four circuits resulted in the removal of leukocytes and platelets, both from septic and healthy blood (Figure 2). This was particularly significant for hemoadsorption, especially with the small beads, where less than 10% of platelets and leukocytes remained circulating at the end of the experiments with septic blood. Importantly, the leukocyte depletion was primarily seen in monocytes and neutrophils whereas lymphocytes showed little affect. The circuit without a blood purification device (sham circuit) was responsible for a slight decrease in leukocytes and platelets. EM and IF images confirmed adsorption of leukocytes and platelets onto the surface of the beads (Figure 3).


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)

Effects of extracorporeal circuits on white blood cells (WBC), neutrophils (PMN), monocytes (Mono), lymphocytes (Lymph) and platelets (Plts). Results are expressed as % of cells present before circulation through the circuits (uncirculated condition), in blood obtained from septic patients and healthy volunteers (medians with interquartile ranges). *P < .05, **P < .01, ***P < .001 compared with Sham.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effects of extracorporeal circuits on white blood cells (WBC), neutrophils (PMN), monocytes (Mono), lymphocytes (Lymph) and platelets (Plts). Results are expressed as % of cells present before circulation through the circuits (uncirculated condition), in blood obtained from septic patients and healthy volunteers (medians with interquartile ranges). *P < .05, **P < .01, ***P < .001 compared with Sham.
Mentions: Blood circulation through all four circuits resulted in the removal of leukocytes and platelets, both from septic and healthy blood (Figure 2). This was particularly significant for hemoadsorption, especially with the small beads, where less than 10% of platelets and leukocytes remained circulating at the end of the experiments with septic blood. Importantly, the leukocyte depletion was primarily seen in monocytes and neutrophils whereas lymphocytes showed little affect. The circuit without a blood purification device (sham circuit) was responsible for a slight decrease in leukocytes and platelets. EM and IF images confirmed adsorption of leukocytes and platelets onto the surface of the beads (Figure 3).

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