Multilateral Functional Alterations of Human Neutrophils in Sepsis: From the Point of Diagnosis to the Seventh Day
Neutrophil functional changes caused by sepsis itself and their time-course variation have not been fully elucidated because previous studies targeted patients who had received therapeutic interventions. We explored the multilateral functions of circulating neutrophils in patients with severe sepsis or septic shock who had not yet undergone interventions, and followed their changes. Patients were treated based on the Surviving Sepsis Campaign Guidelines 2012. Neutrophil functions were evaluated on days 0 (before therapeutic intervention), 3, and 7 in 59 septic patients. The clinical severity score (APACHE II and SOFA) and serum pro-/anti-inflammatory cytokine concentrations of the patients were significantly increased on day 0 and normalized on day 3. However, neutrophil priming state, estimated by measuring the fMLP-stimulated reactive oxygen species, was significantly elevated on day 0, further augmented on day 3, and then returned to day 0 levels on day 7 despite general resolution of the inflammatory response. The expression of CXC chemokine receptor 2 and paired immunoglobulin-like receptor α, assessed as surrogate markers of transmigration and adhesion potency, was suppressed most strongly on day 0 and gradually recovered. To conclude, contrary to the patient's clinical course, neutrophil priming state was augmented most strongly at 3 days after diagnosis of sepsis. Impaired transmigration and excessive adhesion potency were observed most prominently at diagnosis. These observations would partially explain the mechanism of development of multiple organ dysfunction of the host who is subjected to a secondary insult, and may provide an important perspective for the implementation of additional immune-modulating therapy in sepsis.