Systemic Markers of Monocyte Activation in Acute Pulmonary Oedema

Hydrostatic lung injury followed by pulmonary remodelling variably complicates cardiogenic acute pulmonary oedema (APO). Pulmonary remodelling may be regulated by the balance between distinct phenotypes of pulmonary macrophages; activated/inflammatory (M1), and reparative/anti-inflammatory (M2), derived from circulating monocyte populations. The aim of this study was to identify biomarkers in peripheral blood that are consistent with hydrostatic lung injury and pulmonary remodelling in APO and which follow the variable clinical course.

To examine peripheral markers of lung inflammation, resolution and remodelling, 18 patients, admitted to the intensive care unit (ICU) with a clinical diagnosis of APO, were enrolled. Admission, 12- and 24-hour post-admission bloods were assayed for cytokines by ELISA (R&D Systems, Minneapolis, MN, USA) and leukocyte surface markers by flow cytometry.

Admission PaO₂ to FiO₂ ratio was positively correlated with Mon 2 (intermediate) monocyte prevalence, through increasing ratio of CD16⁺ monocytes to CD11b⁺ and CD40⁺ monocytes, and negatively correlated with Mon 1 (classical) monocyte prevalence, through decreasing ratio of CD16⁺ monocytes to CD62L⁺. Secondary cohort analysis compared 10 APO patients with established chronic heart failure (CHF) to eight without CHF. An increase in monocyte chemotactic peptide (MCP)-1, monocyte prevalence, and CD16^-CD62L⁺ monocytes with CHF, all characteristic of monocyte activation to a Mon 1 phenotype, were found in the CHF APO patients.

Increased systemic monocyte prevalence and expression of cell surface markers suggest a Mon 1 profile in CHF patients during episodes of APO. Future studies should define the role of systemic monocyte prevalence and activation in decompensated CHF.