title: Depletion of blood neutrophils from patients with sepsis: treatment for the future?
abstract: 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.
authors.affiliation: Intensive Care Unit, Guy's and St. Thomas' NHS Foundation Trust, London, UK; Vascular Immunology, King's College London, UK.
authors.forename: Sion M
authors.initials: SM
authors.lastname: Lewis
authors.forename: Nahida
authors.initials: N
authors.lastname: Khan
authors.forename: Richard
authors.initials: R
authors.lastname: Beale
authors.forename: David F
authors.initials: DF
authors.lastname: Treacher
authors.forename: K Alun
authors.initials: KA
authors.lastname: Brown
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D018805:Sepsis / Q000276:immunology / Q000628:therapy*
keywords: Neutrophils; adherence; cytokines; leukofiltration; sepsis