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

Thomas Rimmelé,Anan Chuasuwan,Morgan V Fedorchak,Daniel R Frederick,William J Federspiel,John A Kellum,Lin Zhu,Zhiyong Peng,Melinda Carter,Kai Singbartl,Joseph N Mclaughlin,Jeffery V Bishop,Adriana Zeevi,Ata Kaynar

doi:10.1186/cc12587

Thomas Rimmelé, Anan Chuasuwan + Show 12 more

Open Access

https://doi.org/10.1186/cc12587

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Abstract

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. 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. 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. 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.

Highlights

Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis
Hemoadsorption devices were selective for removal of neutophils and monocytes Blood circulation through all four circuits resulted in the removal of leukocytes and platelets, both from septic and healthy blood (Figure 2)
This was 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

Summary

Introduction

Promising preclinical results have been obtained with blood purification therapies as adjuvant treatment for sepsis. The mechanisms by which these therapies exert beneficial effects remain unclear. Care is mostly supportive as specific treatments for sepsis have failed to become universally accepted [2,3,4,5]. Blood purification techniques, including high-volume hemofiltration (HVHF), cascade hemofiltration, hemoadsorption, plasmapheresis, coupled plasma filtration adsorption (CPFA), high-adsorption hemofiltration, and high cut-off hemodialysis/hemofiltration, represent a class of therapies for sepsis that have seen promising pre-clinical. There are no large multicenter trials evaluating the ability of blood purification therapies to improve patient-centered outcomes in sepsis. The mechanisms by which these therapies exert beneficial effects remain poorly understood and controversial [16]

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