TNFα release by monocyte-derived macrophages at stable and exacerbation states in COPD

Inflammation is a hallmark of COPD and contributes to its pathogenesis. Inflammatory cells, such as alveolar macrophages, release inflammatory mediators including TNFα. We investigated basal and bacteria stimulated TNFα release by monocyte-derived macrophages (MDMs) at stable and exacerbation states. MDMs were cultured from 26 COPD patients at paired stable and exacerbation states. The MDMs were incubated for 4 h at 37 o C with 100μl of RPMI (controls), inert beads (4.5x10 9 microspheres/ml), or heat-killed Haemophilus influenzae (HI) or Streptococcus pneumoniae (SP) (both at 5x10 8 cfu/ml). Subsequent TNFα release was measured by ELISA. There was no difference in basal TNFα release from MDMs at stable and exacerbation states (p=0.247). There was a significant difference in TNFα release between the inert beads, HI and SP (p 0.05). In response to SP, TNFα release significantly increased at exacerbation compared to stable state (p=0.007, Figure 1A), but not in response to HI (p=0.513, Figure 1B). HI is more pro-inflammatory than SP at both stable and exacerbation COPD states. However, a significant increase in TNFα release from stable to exacerbation state is only seen in response to SP. Further work is needed to investigate this response and the relationship with phagocytosis.