Dysfunction of alveolar macrophages after 3 cardiac surgery and postoperative pneumonia? – an 5 observational study

Abstract

IntroductionPatients undergoing cardiac surgery have an increased risk of postoperative pneumonia. Pulmonary immune dysfunction might be a contributing factor. We therefore determined changes of the surface molecules on alveolar macrophages (AMs). To characterize modulation in patients with pneumonia we correlated these changes to the development of postoperative pneumonia.MethodsAfter ethical approval and written informed consent, 33 patients undergoing elective coronary bypass grafting surgery were included in this observational study. Peripheral blood cells and alveolar lavage fluid were collected directly after induction of anesthesia and two hours after separation from cardiopulmonary bypass (CPB). Human leukocyte antigen-DR (HLA-DR) and toll-like receptors (TLR) 2/4 expression on monocytes and AM were assessed by flow cytometry. A total of three patients developed postoperative pneumonia determined according to the criteria of the Center of Disease Control. Statistical analysis was performed with the Mann–Whitney-U test and Wilcoxon test.ResultsWe found significant changes of phenotypic and functional immune markers on AMs after cardiac surgery. HLA-DR expression on peripheral blood monocytes and AMs was significantly reduced compared to baseline in all patients (each approximately 30%). After surgery patients who developed postoperative pneumonia revealed a trend of stronger reduction of HLA-DR expression (83.7% versus 27.1%) and TLR4 expression on AMs (46.1% versus 9.9%) compared to patients without pneumonia. Already before surgery, the baseline of TLR2 expression on AM was significantly lower (27.7%) in patients who developed postoperative pneumonia.ConclusionsAs far as we know this is the first study that shows an early impairment of lung cellular immune response after cardiac surgery. These findings can help to understand the role of cell-mediated immunosuppression and its association to the development of postoperative pneumonia.

Lung cell-specific modulation of LPS-induced TLR4 receptor and adaptor localization

“…Patients who postoperatively developed pneumonia revealed a stronger reduction of TLR4 expression on alveolar macrophages than patients who did not 93 suggesting that a local cell-mediated immunosuppression in the lung might be a risk factor for postoperative pneumonia. The expression of TLR4 on alveolar macrophages from patients with ARDS is suppressed and, compared with control cells, does not change after ex vivo stimulation of the cells with LPS 94 .…”

Immune Dysfunction After Cardiac Surgery with Cardiopulmonary Bypass

“…In a prospective study, Chalk et al have also reported a dysfunction of pulmonary macrophages after CPB. In particular, they have described an early impairment of lung cellular immune response, which could promote the development of postoperative pneumonia [6]. Along these lines, a downregulation of human leucocyte antigen-DR antigen (HLA-DR) expression on monocytes and an increase of plasma interleukine (IL)-10 associated with the occurrence of nosocomial infections have been reported [4,6,7].…”

Monocyte hyporesponsiveness and Toll-like receptor expression profiles in coronary artery bypass grafting and its clinical implications for postoperative inflammatory response and pneumonia

“…42 More recent, Chalk et al 43 found a trend towards intraoperative decreases in TLR-2 and TLR-4 expression on alveolar macrophages in CABG patients diagnosed with postoperative pneumonia. This has already been demonstrated in surgical ICU patients, in whom LPS tolerance was related to worse clinical outcomes.…”