Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by neutrophilic inflammation in the airways and these cells contribute to the production of inflammatory mediators. Dampening the production of pro-inflammatory mediators might be an important strategy to treat COPD and glucocorticosteroids are known to do so via inhibition of NF-κB. However, this pathway is important for the control of pro- and anti-inflammatory genes. Therefore, we studied the effects of dexamethasone on production and secretion of pro-inflammatory IL-1β and anti-inflammatory sIL-1Ra by human neutrophils activated with TNFα.
In vitro, TNFα-stimulated neutrophils produced significant amounts of IL-1β and sIL-1Ra, which was inhibited by dexamethasone. However, synthesis and secretion of sIL-1Ra was inhibited at lower concentrations dexamethasone compared to IL-1β which changed the IL-1β: sIL-1Ra ratio significantly. This changed ratio resulted in a more pro-inflammatory condition as visualized by increased ICAM-1 expression on human endothelial cells. In vivo, moderate–to-severe COPD patients using inhaled glucocorticosteroids have decreased plasma sIL-Ra levels compared to mild-to-moderate patients not on glucocorticosteroid treatment.
In conclusion, dexamethasone induces a pro-inflammatory shift in the IL-1β:sIL-1Ra cytokine balance in neutrophils in vitro which might contribute to a lack of endogenous anti-inflammatory signals to dampen inflammation in vivo.
- ERS
