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Steroids induce a disequilibrium of sIL-1Ra and IL-1β synthesis by human neutrophils

J.D. Langereis, E-J. Oudijk, R.C. Schweizer, J-W.J. Lammers, L. Koenderman, L.H. Ulfman
European Respiratory Journal 2010; DOI: 10.1183/09031936.00170409
J.D. Langereis
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E-J. Oudijk
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R.C. Schweizer
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J-W.J. Lammers
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L. Koenderman
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L.H. Ulfman
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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.

  • COPD
  • glucocorticosteroids
  • interleukin-1β
  • interleukin-1 receptor antagonist
  • neutrophil
  • ERS
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Steroids induce a disequilibrium of sIL-1Ra and IL-1β synthesis by human neutrophils
J.D. Langereis, E-J. Oudijk, R.C. Schweizer, J-W.J. Lammers, L. Koenderman, L.H. Ulfman
European Respiratory Journal Jan 2010, erj01704-2009; DOI: 10.1183/09031936.00170409

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Steroids induce a disequilibrium of sIL-1Ra and IL-1β synthesis by human neutrophils
J.D. Langereis, E-J. Oudijk, R.C. Schweizer, J-W.J. Lammers, L. Koenderman, L.H. Ulfman
European Respiratory Journal Jan 2010, erj01704-2009; DOI: 10.1183/09031936.00170409
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