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

•Neutrophils are implicated in the organ failure of severe sepsis.•Increased expression of adhesion molecules on neutrophils from patients with sepsis enhances binding to endothelial cells.•Augmented neutrophil attachment to microvascular endothelium and impaired chemotaxis may contribute to vascular damage.•Neutrophils are a potent source of pro-inflammatory cytokines in sepsis.•Depletion of neutrophils may improve organ function in patients with severe sepsis.•Targeting neutrophil subpopulations that promote organ damage could be of therapeutic benefit for patients with sepsis.

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.