Depletion of blood neutrophils from patients with sepsis: Treatment for the future?

TY - JOUR

T1 - Depletion of blood neutrophils from patients with sepsis

T2 - Treatment for the future?

AU - Lewis, Sion M.

AU - Khan, Nahida

AU - Beale, Richard

AU - Treacher, David F

AU - Brown, K. Alun

N1 - © 2013 Elsevier B.V.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Organ failure arising from severe sepsis accounts for nearly 6 million deaths worldwide per annum. At present there are no specific pharmacological agents available for its treatment and identifying a suitable therapeutic target is urgently needed. Neutrophils appear to be contributing directly to pulmonary damage in severe forms of lung injury and indirectly to the failure of other organs. Blood neutrophils from patients with sepsis possess a phenotype that is indicative of activation and our results show that neutrophils isolated from patients with sepsis exhibit a supranormal adherence to endothelial monolayers treated with pro-inflammatory cytokines. Additional studies reveal that the patients' cells are highly efficient at releasing IL-8. We also demonstrate that organ function is improved upon removing neutrophils from the circulation. In this article we propose that in severe sepsis there is a subpopulation of neutrophils which is actively engaged in pathological insult. The phenotypic characterisation of this subset may provide a novel therapeutic strategy for sepsis that could lead to patient benefit.

AB - Organ failure arising from severe sepsis accounts for nearly 6 million deaths worldwide per annum. At present there are no specific pharmacological agents available for its treatment and identifying a suitable therapeutic target is urgently needed. Neutrophils appear to be contributing directly to pulmonary damage in severe forms of lung injury and indirectly to the failure of other organs. Blood neutrophils from patients with sepsis possess a phenotype that is indicative of activation and our results show that neutrophils isolated from patients with sepsis exhibit a supranormal adherence to endothelial monolayers treated with pro-inflammatory cytokines. Additional studies reveal that the patients' cells are highly efficient at releasing IL-8. We also demonstrate that organ function is improved upon removing neutrophils from the circulation. In this article we propose that in severe sepsis there is a subpopulation of neutrophils which is actively engaged in pathological insult. The phenotypic characterisation of this subset may provide a novel therapeutic strategy for sepsis that could lead to patient benefit.

KW - adherence

KW - cytokines

KW - leukofiltration

KW - Neutrophils

KW - sepsis

UR - http://www.scopus.com/inward/record.url?scp=84890129429&partnerID=8YFLogxK

U2 - 10.1016/j.intimp.2013.10.002

DO - 10.1016/j.intimp.2013.10.002

M3 - Article

C2 - 24144812

AN - SCOPUS:84890129429

SN - 1567-5769

VL - 17

SP - 1226

EP - 1232

JO - INTERNATIONAL IMMUNOPHARMACOLOGY

JF - INTERNATIONAL IMMUNOPHARMACOLOGY

IS - 4

ER -