Coronary artery bypass grafting is associated with immunoparalysis of monocytes and dendritic cells

Abstract

Coronary artery bypass grafting (CABG) triggers a systemic inflammatory response that may contribute to adverse outcomes. Dendritic cells (DC) and monocytes are immunoregulatory cells potentially affected by CABG, contributing to an altered immune state. This study investigated changes in DC and monocyte responses in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 and day 5. Whole blood from 49 CABG patients was used in an ex vivo whole blood culture model to prospectively assess DC and monocyte responses. Lipopolysaccharide (LPS) was added in parallel to model responses to an infectious complication. Co-stimulatory and adhesion molecule expression and intracellular mediator production was measured by flow cytometry. CABG modulated monocyte and DC responses. In addition, DC and monocytes were immunoparalysed, evidenced by failure of co-stimulatory and adhesion molecules (eg HLA-DR), and intracellular mediators (eg IL-6) to respond to LPS stimulation. DC and monocyte modulation was associated with prolonged ICU length of stay and post-operative atrial fibrillation. DC and monocyte cytokine production did not recover by day 5 post-surgery. This study provides evidence that CABG modulates DC and monocyte responses. Using an ex vivo model to assess immune competency of CABG patients may help identify biomarkers to predict adverse outcomes. K E Y W O R D Scardiac surgery, coronary artery bypass, Dendritic cells, immune modulation, immunoparalysis, monocytes

Current Understanding of Leukocyte Phenotypic and Functional Modulation During Extracorporeal Membrane Oxygenation: A Narrative Review

“…definition of innate immunoparalysis mediated by ECMO ( 92 ). The observed changes are also in line with profiles associated with sepsis, and nosocomial infections in post-CPB cardiac surgery and VAD implanted patients ( 40 , 41 , 49 ).…”

“…Existing research reported alteration of leukocyte numbers, phenotype, and functions with non-specific activation when ECMO is used ( Tables 1 and 2 ). A similar response has been observed in other extracorporeal circulatory modalities preceding ECMO, such as cardiopulmonary bypass (CPB), renal replacement therapy, and ventricular assist devices (VAD) ( 40 – 49 ). The sequelae linked to inappropriate leukocyte modulation can be detrimental.…”

“…It can occur within 2 h of ECMO cannulation ( 13 , 14 , 22 ). In contrast to CPB where the number of leukocytes increased during open heart surgeries ( 40 , 43 ), leukocytopenia has long been reported in ECMO ( 16 , 25 ). Differences could be associated with the pathophysiology between ECMO and CPB patients, and the involvement of other immune triggers (e.g.…”

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“…Dendritic cells are important regulatory immune cells at the interface of the innate and adaptive immune system. The ability of dendritic cells to produce cytokines and express activation and co-stimulatory markers confirms immune competence 24 . Dendritic cell immune profile was assessed following exposure of the patient’s preoperative blood to ABT or their own ICS.…”

DataSheet_1.pdf

“…Existing research reported alteration of leukocyte numbers, phenotype, and functions with non-specific activation when ECMO is used (Tables 1 and 2). A similar response has been observed in other extracorporeal circulatory modalities preceding ECMO, such as cardiopulmonary bypass (CPB), renal replacement therapy, and ventricular assist devices (VAD) (40)(41)(42)(43)(44)(45)(46)(47)(48)(49). The sequelae linked to inappropriate leukocyte modulation can be detrimental.…”