Recombinant GM-CSF enhances the bactericidal ability of PMNs by increasing intracellular IL-1ß and improves the prognosis of secondary Pseudomonas aeruginosa pneumonia in sepsis
This study tested the hypothesis that recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) enhances polymorphonuclear neutrophils (PMNs) via IL-1ß to improve the prognosis of secondary infection in sepsis. The latter stage of sepsis is prone to induce immunosuppression, resulting in secondary fatal infections. rGM-CSF has become a way for sepsis-induced immunosuppression due to its immunomodulatory effect. However, the functional impact of GM-CSF on PMNs in sepsis remains obscure. This study aimed to study the role of rGM-CSF on the bactericidal ability of PMNs in septic mice, assessing its effect on the prognosis of secondary pneumonia, and explore the mechanism of rGM-CSF by intervening PMNs in patients with sepsis. The C57BL/6J sepsis mouse model was induced by cecal ligation and puncture (CLP). rmGM-CSF was used in vivo when mice developed immunosuppression, which was characterized by abnormal bactericidal function of PMNs in peripheral blood. rmGM-CSF improved the prognosis of secondary pneumonia and reversed the function of PMNs. PMNs isolated by Percoll from septic patients were treated by rhGM-CSF in vitro. The expression of CD11b, reactive oxygen species (ROS), phagocytosis and neutrophil extracellular traps (NETs) release in PMNs were enhanced by rhGM-CSF treatments. Whole-transcriptomic sequencing of mouse PMNs indicated that recombinant GM-CSF increased the expression of il1b gene in PMNs. Blocking and inhibiting IL-1ß release effectively counteracted the enhancing effect of GM-CSF on the bactericidal function of PMNs. RmGM-CSF enhances the bactericidal function of PMNs in vivo and improves the prognosis of secondary pneumonia in septic mice, and recombinant GM-CSF increases IL-1ß precursor reserves, which, if stimulated, can rapidly enhance the bactericidal capacity of PMNs. Overall design: Comparative gene expression profiling analysis of RNA-seq data for mice peripheral blood PMNs from three groups (sham operation group, CLP 5days group and CLP5days +GM-CSF groups).