Possible role of M-CSF and GM-CSF in the pathogenesis of chronic obstructive pulmonary disease

Introduction. Granulocyte-macrophage (GM-CSF) and macrophage (M-CSF) colony-stimulating factors are produced by various cells and regulate the proliferation and differentiation of monocytes and macrophages. Concentrations of these substances may vary significantly in many diseases including chronic obstructive pulmonary disease (COPD). Aim. To analyze the concentrations of GM-CSF and M-CSF in the blood plasma of COPD patients and individuals without bronchial obstruction and to determine the patterns of change in these factors in COPD. Materials and methods. The study included 53 smokers with COPD and 24 subjects without bronchial obstruction of which 46% were smokers. Parameters of lung function were measured by spirometry. The concentrations of GM-CSF and M-CSF were determined in the blood plasma using enzyme-linked immunosorbent assay. Cytokines (interleukin (IL)-4, IL-2, IL-1β, tumor necrosis factor (TNF)-α, chemokine C-C motif ligand (CCL) 2, C-X-C chemokine (CXCL)-10, IL-17A, IL-6, IL-10, interferon (IFN)-γ, IL-12p70, IL-8) were determined by multiplex immunofluorescence analysis. Results. The level of M-CSF was significantly reduced in patients with COPD compared to the control group (0.99 (0.39-2.10) pg/ml vs. 2.18 (0.55-3.43) pg/ml, p= 0.04). The median value of GM-CSF, on the contrary, was higher in COPD, although the differences with the control group were not significant (0.57 (0.0-2.49) pg/ml vs. 0.28 (0.0-1.81) pg/ml, p=0.73). The GM-CSF/M-CSF ratio was 0.17 (0.0-2.30) in patients with COPD and 0.15 (0.0-0.80) in those without bronchial obstruction (p=0.85). Concentrations of M-CSF and GM-CSF did not correlate with each other, and were also not associated with age, smoking index, and lung function parameters. Direct correlations were revealed between GM-CSF and percentage of circulating classical monocytes in COPD (ρ=0.38, p=0.008). Conclusion. Considering the important role of M-CSF in the differentiation of anti-inflammatory M2 macrophages, a decrease in the level of this factor may be associated with pro-inflammatory cell polarization in COPD.

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