Differential response of monocyte-derived macrophages from COPD and healthy subjects to LPS/IFN? stimulation

Abstract

Background: Macrophages play important role in COPD pathogenesis. Some studies showed that COPD macrophages may have pro-inflammatory biased phenotype however the results are contradictory.

Objectives: The aim of the study was to compare the response of monocyte-derived macrophages from COPD and healthy subjects to LPS/IFNγ stimulation in terms of cytokines production.

Methods: Macrophages were differentiated in vitro from monocytes obtained from six COPD patients and six healthy subjects in presence of 50 ng/ml GM-CSF. After that, the cells were stimulated with LPS/IFNγ for 24 h. Cytokines were measured in cell culture supernatants by multiplex assay using flow cytometer.

Results: We found that in response to the pro-inflammatory stimulation macrophages obtained from COPD patients produced more CXCL10 and less IL-10 as compared to the cells from healthy subjects. In COPD, there was a 104.5 (51.3-187.4)-fold increase in CXCL10 level (from 59.5 (27.9-124.1) to 8897.9 (2996.6-9392.5) pg/ml) while in controls it was increased only 41.6 (8.1-55.5)-fold (from 93.8 (6.3-149.4) to 3739.6 (33.5-8289.3) pg/ml). At the same time, IL-10 production increased 30.5 (8.5-42.7)-fold in COPD (from 5.7 (3.0-9.2) to 86.5 (26.0-524.3) pg/ml) and 99.6 (71.2-135.8)-fold in healthy subjects (from 4.6 (3.6-5.5) to 355.3 (79.8-751.2) pg/ml). Significance levels (p) of the difference between fold-change parameters were 0.04 and 0.06 for CXCL10 and IL-10 respectively.

Conclusions: The results suggest that macrophages from COPD patients may be predisposed to exaggerated production of pro-inflammatory CXCL10 and reduced secretion of anti-inflammatory IL-10 and thus contribute to COPD pathogenesis.