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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 cytokine concentrations, in septic and healthy blood. Data are expressed as % of the uncirculated condition (medians with interquartile ranges). GM-CSF, granulocyte macrophage colony stimulating factor; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor. *P < .05, **P < .01, ***P < .001 compared with Sham.
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Figure 4: Effects of extracorporeal circuits on cytokine concentrations, in septic and healthy blood. Data are expressed as % of the uncirculated condition (medians with interquartile ranges). GM-CSF, granulocyte macrophage colony stimulating factor; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor. *P < .05, **P < .01, ***P < .001 compared with Sham.

Mentions: Compared to baseline, hemofiltration and hemoadsorption decreased the concentration of IL-6 and IL-10 in septic blood (Figure 4). As expected, cytokine levels in healthy volunteers were very low. A significant production of IL-8 and TNF occurred with the large bead hemoadsorption device; levels increased in both septic and healthy blood. Although changes in TNF were statistically significant, levels were quite low, especially in septic blood (< 10 pg/ml). However, IL-8 levels increased dramatically, exceeding 1,000 pg/ml in both septic and healthy blood. IFN-γ, IL-2, IL-4 and IL-5 levels did not change after circulation through the devices. Neutrophils and monocytes remaining in circulation at the end of the experiment with hemoadsorption were less likely to express CD11b (Figure 5). By contrast, molecules expressed on the surface of lymphocytes were not changed after blood purification using the different devices.


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 cytokine concentrations, in septic and healthy blood. Data are expressed as % of the uncirculated condition (medians with interquartile ranges). GM-CSF, granulocyte macrophage colony stimulating factor; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor. *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 4: Effects of extracorporeal circuits on cytokine concentrations, in septic and healthy blood. Data are expressed as % of the uncirculated condition (medians with interquartile ranges). GM-CSF, granulocyte macrophage colony stimulating factor; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor. *P < .05, **P < .01, ***P < .001 compared with Sham.
Mentions: Compared to baseline, hemofiltration and hemoadsorption decreased the concentration of IL-6 and IL-10 in septic blood (Figure 4). As expected, cytokine levels in healthy volunteers were very low. A significant production of IL-8 and TNF occurred with the large bead hemoadsorption device; levels increased in both septic and healthy blood. Although changes in TNF were statistically significant, levels were quite low, especially in septic blood (< 10 pg/ml). However, IL-8 levels increased dramatically, exceeding 1,000 pg/ml in both septic and healthy blood. IFN-γ, IL-2, IL-4 and IL-5 levels did not change after circulation through the devices. Neutrophils and monocytes remaining in circulation at the end of the experiment with hemoadsorption were less likely to express CD11b (Figure 5). By contrast, molecules expressed on the surface of lymphocytes were not changed after blood purification using the different devices.

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