Granulocyte-macrophage colony-stimulating factor (GM-CSF) restores decreased HLA-DR expression on monocytes after cardiopulmonary bypass

Background: Cardiopulmonary bypass (CPB) is associated with impaired immune response, including diminished monocyte HLA-DR expression and release of pro- and anti-inflammatory cytokines, factors related to the postoperative systemic inflammatory response syndrome and to decreased monocyte and polymorphonuclear neutrophil functions. This leads to increased susceptibility to infections. We investigated monocyte HLA-DR expression in patients undergoing CPB and investigated the impact of the immunostimulating hematopoietic growth factor Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in vitro.

Methods: In 17 patients undergoing elective heart surgery with CPB HLA-DR expression on monocytes, B- and T-lymphocytes was measured before, immediately after CPB, and on the 2nd and 10th postoperative day by flow cytometry. In vitro GM-CSF treatment was performed on whole blood cultures with 100 ng/ml recombinant human GM-CSF for 20h.

Results: Immediately after CPB, monocyte HLA-DR expression was attenuated (124.67±15.26 MFI vs. 143.44±3.94 mean fluorescence intensity (MFI) preoperatively, mean±SD, p<.0001). On the 2nd postoperative day, HLA-DR expression continued to decrease and did not normalize until the 10th postoperative day. In contrast, T-cell HLA-DR expression was not changed, while B-cell HLA-DR decreased on the 2nd postoperative day (151.64±8.32 MFI vs. 170.38±8.63 MFI preoperatively, mean±SD, p<.0001). Under in vitro GM-CSF treatment, HLA-DR expression on monocytes prepared after CPB increased to a degree comparable to preoperative values.

Conclusions: Immune suppression after cardiac surgery is reflected by prolonged diminished monocyte HLA-DR expression. This is not irreversible but can – at least in vitro – be overridden by the immunostimulating compound GM-CSF.