Induced interleukin-19 contributes to cell-mediated immunosuppression in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass

Abstract

Background: Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) promotes immunosuppression, which predisposes patients to infectious complications. We investigated the role of interleukin (IL)-19 in the functions of CD4+ T cells in patients undergoing CABG with CPB.

Methods: Blood samples were withdrawn from 42 patients undergoing elective CABG with CPB. Serum levels of IL-19 were analyzed by enzyme-linked immunosorbent assay (ELISA). The CD4+/CD25+ T-cell population was determined with flow cytometry. Isolated CD4+ T cells were cultured and assayed for proliferation and cytokine production under phorbol myristate acetate/ionomycin stimulation. Cytokine production and Foxp3 mRNA expression in CD4+ T cells from healthy volunteers with or without IL-19 treatment were determined with ELISA and real-time polymerase chain reaction, respectively.

Results: Proliferation percentages were 162%, 48%, 34%, and 39%, and interferon (IFN)-γ production was 1.22 ng/mL, 0.56 ng/mL, 0.33 ng/mL, and 0.35 ng/mL in the CD4+ T cells of patients before CPB and at 24 hours, 48 hours, and 96 hours, respectively, after CPB. Serum levels of IL-19 were higher but negatively correlated with CD4+ T-cell proliferation and IFN-γ production. The populations of CD4+/CD25+ T cells and expression of Foxp3 mRNA in T cells were higher and were positively correlated with IL-19 levels after CPB. Treatment with IL-19 reduced T-cell proliferation and IFN-γ production, increased Foxp3 mRNA expression, and induced the regulatory activity of CD4+ T cells.

Conclusions: Interleukin-19 reduces T-cell responses and promotes the regulatory activity of CD4+ T cells. Induced IL-19 in patients undergoing CABG with CPB contributes to cell-mediated immunosuppression.