Interferon-γ and interleukin-17A associations with vascular dysfunction following paediatric cardiac surgery with cardiopulmonary bypass

Abstract Background: Cardiopulmonary bypass-induced inflammation is associated with poor postoperative outcomes. Bypass exposure has been associated with shifts in lymphocyte populations. This study aimed to describe two cytokine profiles associated with T and NK cells and their effects on clinical markers of postoperative cardiovascular dysfunction in children undergoing cardiac surgery with cardiopulmonary bypass. Methods: Children from two major children’s hospitals undergoing corrective cardiac surgery with cardiopulmonary bypass were included. Plasma was collected pre-, 0 to 4 hours post- and 24 hours (when available) postoperatively. Plasma concentrations of cytokines were quantified using enzyme-linked immunosorbent assays. Delta cytokine concentrations were compared to vasoactive infusion score and percent fluid balance on postoperative day one. Vascular reactivity was assessed in a subset of the cohort. Confirmation of endothelial-specific effects of interferon-γ and interleukin-17A was performed in microvascular endothelial cells, assessing cytokine levels by enzyme-linked immunosorbent assays or trans-endothelial electrical resistance. Results: A total of 26 children were included in the analysis. Interferon-γ was inversely associated with vasoactive infusion score ( p < 0.05), whereas interleukin-17A and interleukin-23 were associated with greater cumulative postoperative fluid balance ( p < 0.01 and 0.03, respectively). Peak vascular reactivity is strongly associated with interferon-γ ( p = 0.001), but not with circulating interleukin-17A. Human microvascular endothelial cell exposure to interferon-γ increased endothelial permeability and cytokine production. Conclusions: Interferon-γ and interleukin-17A may be associated with cardiovascular dysfunction in children after exposure to cardiopulmonary bypass, albeit with differential clinical features. Interferon-γ may directly impact vascular measures, while the impact of interleukin-17A may relate to fluid accumulation.