Whole blood transcriptomics reveals granulocyte colony‐stimulating factor as a mediator of cardiopulmonary bypass‐induced systemic inflammatory response syndrome

• DOI: 10.1002/cti2.1490
• Publication Date: 2024-02-19T08:16:25Z
• Authors: Katherine R Martin; Cristina Gamell; Tsin Yee Tai; Roberto Bonelli; Jacinta Hansen; James Tatoulis; Monther Alhamdoosh; Nicholas Wilson; Ian Wicks
• Keywords: 0301 basic medicine; 0303 health sciences; 610; whole blood transcriptomics; RC581-607; cytokines; granulocyte colony‐stimulating factor; systemic inflammatory response syndrome; Original Article; Immunologic diseases. Allergy; cardiopulmonary bypass; cell‐free DNA

Abstract Objectives Systemic inflammatory response syndrome (SIRS) is a frequent complication of cardiopulmonary bypass (CPB). SIRS associated with significant morbidity and mortality, but its pathogenesis remains incompletely understood, as result, biomarkers are lacking treatment expectant supportive. This study aimed to understand the pathophysiological mechanisms driving induced by CPB identify novel therapeutic targets that might reduce systemic inflammation improve patient outcomes. Methods Twenty‐one patients undergoing cardiac surgery were recruited, blood was sampled before, during after surgery. defined using American College Chest Physicians/Society Critical Care Medicine criteria. We performed immune cell profiling whole transcriptomics measured individual mediators in plasma/serum characterise CPB. Results Nineteen fulfilled criteria for SIRS, mean duration 2.7 days. Neutrophil numbers rose rapidly remained elevated at least 48 h afterwards. Transcriptional signatures neutrophil activation degranulation enriched identified network cytokines governing these transcriptional changes, including granulocyte colony‐stimulating factor (G‐CSF), regulator production function. Conclusions neutrophils G‐CSF major regulators CPB‐induced inflammation. Short‐term targeting could provide strategy limit neutrophil‐mediated tissue damage