TY - JOUR T1 - Steroids induce a disequilibrium of sIL-1Ra and IL-1β synthesis by human neutrophils JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/09031936.00170409 SP - erj01704-2009 AU - J.D. Langereis AU - E-J. Oudijk AU - R.C. Schweizer AU - J-W.J. Lammers AU - L. Koenderman AU - L.H. Ulfman Y1 - 2010/01/01 UR - http://erj.ersjournals.com/content/early/2010/07/22/09031936.00170409.abstract N2 - 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. ER -