Imbalance of M1/M2 alveolar macrophages phenotype in bronchial asthma (LB506)

Abstract

This study evaluated imbalance of M1/M2 alveolar macrophages (AM) phenotype in BA of various state and healthy volunteers (HV). Methods: In bronchoalveolar lavage fluid (BALF) and culture medium of AM in patients with intermittent BA (iBA) (n=15, 46,56±4,18 y.o.), persistent BA (pBA) (n=15, 48,24±3,27 y.o) and HV (n=10, 51,83±3,52 y.o.) AM phenotype was assessed by flow cytometry (Beckman Coulter FC500) by production of proinflammatory M1 cytokines: IL‐1β, IL‐8, IL‐12p70, IFN‐γ, TNF‐α and TNF‐β; anti‐inflammatory М2 cytokines: IL‐4, IL‐5 and IL‐10, and bivalent М1/М2 cytokines: IL‐2 and IL‐6. Results: Analysis of BALF cytokine profile in iBA and pBA identified evident imbalance of pulmonary immune response towards M2 phenotype as compared to HV. Generalized M1/M2 indices in iBA and pBA were comparable ‐ 0.84 and 0.88. The value of M1/M2 index in healthy persons was assumed equal to 1. Genuine AM phenotype assessed by cytokine production in culture medium revealed significant changes in BA regardless of the disease state. In both iBA and pBA M1/M2 indices changed towards M1 vs. HV (4.68 and 1.59, respectively). Conclusions: Analysis of cytokine pattern in bronchoalveolar lavage fluid and culture medium of alveolar macrophages in bronchial asthma revealed imbalance of M1/M2 alveolar macrophages phenotype and local pulmonary immune response. Shift of genuine alveolar macrophages phenotype towards M1, probably, reflect common proinflammatory component of the disease and contribute to asthma exacerbation. Drift of cytokine pattern in BALF towards M2 phenotype most likely indicate compensatory reaction of alveolar macrophages and of the innate immune response.