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

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.