Differential cigarette smoke and H₂O₂induced cytokine release from macrophages in COPD

Macrophages (MΦ) are increased in COPD but are dysfunctional, possibly due to oxidative stress. To investigate this, monocyte derived MΦ (MDM) and tissue MΦ were exposed to cigarette smoke extract (CSE) or H₂O₂. MDM from non-smokers (NS), smokers (S) and COPD (n=4-8) were differentiated in GM or M-CSF. TMΦ were isolated from resected tissue (n=2-5). Cells were exposed to 30-300µM H₂O₂ or 10-100% CSE ± 10ng/ml LPS for 24h. Cell viability was determined by MTT assay and cytokine release (CXCL8, TNFα, IL6, CCL2, IL10) by ELISA. H₂O₂ and CSE stimulated only CXCL8 release from all MDM (Table 1). CSE stimulated CXCL8 release from COPD TMΦ only. CSE inhibited LPS-stimulated release of TNFα, IL6, CCL2 and IL10 from all MΦ types. CSE and LPS were additive with CXCL8 from MDM but the opposite in TMΦ. Cytokine release from MΦ differed with CSE or H₂O₂ with discrepancies between MDM and TMΦ.