Whole blood transcriptomics reveals G-CSF as a mediator of cardiopulmonary bypass- induced systemic inflammatory response syndrome
Objectives: Systemic inflammatory response syndrome (SIRS) is a frequent complication of cardiopulmonary bypass (CPB). SIRS is associated with significant morbidity and mortality, but its pathogenesis remains incompletely understood, and as a result biomarkers are lacking, and treatment remains expectant and supportive. This study aimed to understand the pathophysiological mechanisms driving SIRS induced by CPB and identify novel therapeutic targets that might reduce systemic inflammation and improve patient outcomes. Methods: 21 patients undergoing cardiac surgery and CPB were recruited, and blood was sampled before, during and after surgery. SIRS was defined using the American College of Chest Physicians/Society of Critical Care Medicine criteria. We performed immune cell profiling, whole blood transcriptomics and measured individual mediators in plasma/serum to characterise SIRS induced by CPB. Results: Nineteen patients fulfilled criteria for SIRS, with a mean duration of 2.7 days. Neutrophil numbers rose rapidly with CPB and remained elevated for at least 48 hours afterwards. Transcriptional signatures associated with neutrophil activation and degranulation were enriched during CPB. We identified a network of cytokines governing these transcriptional changes, including granulocyte colony stimulating factor (G-CSF), a regulator of neutrophil production and function. Conclusions: We identified neutrophils and G-CSF as major regulators of CPB induced systemic inflammation. Short-term targeting of G-CSF could provide a novel therapeutic strategy to limit neutrophil mediated inflammation and tissue damage in SIRS induced by CPB. Overall design: Venous blood was sampled pre and postoperatively and venous and arterial blood was collected after 60 mins on CPB. Blood was collected into PAXgene Blood RNA collection tubes (PreAnalytiX GmbH, Hombrechtikon, Switzerland), which were stored at -20°C until RNA was extracted Groups: PRE, Day_1, 60A (arterial line), 60V (venous line).