Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1β synthesis by human neutrophils
Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1β synthesis by human neutrophils
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DOI：
10.1183/09031936.00170409
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发表时间：
2011-02-01
影响因子：
24.3
通讯作者：
Ulfman, L. H.
中科院分区：
文献类型：
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作者：
Langereis, J. D.;Oudijk, E-J. D.;Ulfman, L. H.
慢性阻塞性肺疾病（COPD）的特征是气道中的中性粒细胞炎症，这些中性粒细胞有助于炎症介质的产生。抑制促炎介质的产生可能是治疗 COPD 的重要策略，而已知糖皮质激素通过抑制核因子 kappa B 来实现这一点。然而，该途径对于促炎和抗炎基因的控制很重要。我们研究了地塞米松对用 2 激活的人中性粒细胞产生和分泌促炎白细胞介素 (IL)-1 β 和抗炎分泌型 IL-1 受体拮抗剂 (sIL-1Ra) 的影响。肿瘤坏死因子 (TNF)-α。在体外，TNF-α 刺激的中性粒细胞产生大量的 IL-1β 和 sIL-1Ra；这种产生受到地塞米松的抑制。然而，与IL-1β相比，较低浓度的地塞米松会抑制sIL-1Ra的合成和分泌，这显着改变了IL-1β：sIL-1Ra的比率。这种比例的改变导致了更加促炎的情况，正如人内皮细胞上细胞间粘附分子 1 表达增加所显示的那样。在体内，与未接受糖皮质激素治疗的轻度至中度患者相比，使用吸入糖皮质激素的中度至重度 COPD 患者血浆 sIL-Ra 水平降低。 总之，地塞米松在体外诱导中性粒细胞中 IL-1β:sIL-1Ra 细胞因子平衡的促炎性转变，这可能导致体内缺乏内源性抗炎信号来抑制炎症。
Chronic obstructive pulmonary disease (COPD) is characterised by neutrophilic inflammation in the airways and these neutrophils contribute to the production of inflammatory mediators. Dampening the production of proinflammatory mediators might be an important strategy to treat COPD and glucocorticosteroids are known to do so via inhibition of nuclear factor-kappa B. However, this pathway is important for the control of pro- and anti-inflammatory genes.We studied the effects of dexamethasone on production and secretion of pro-inflammatory interleukin (IL)-1 beta and anti-inflammatory secreted IL-1 receptor antagonist (sIL-1Ra) by human neutrophils activated with tumor necrosis factor (TNF)-alpha.In vitro, TNF-alpha-stimulated neutrophils produced significant amounts of IL-1 beta and sIL-1Ra; this production was inhibited by dexamethasone. However, synthesis and secretion of sIL-1Ra was inhibited at lower concentrations dexamethasone compared to IL-1 beta, which changed the IL-1 beta: sIL-1Ra ratio significantly. This altered ratio resulted in a more pro-inflammatory condition, as visualised by increased intercellular adhesion molecule-1 expression on human endothelial cells. In vivo, moderate-to-severe COPD patients using inhaled glucocorticosteroids have decreased plasma sIL-Ra levels compared with mild-to-moderate patients not on glucocorticosteroid treatment.In conclusion, dexamethasone induces a pro-inflammatory shift in the IL-1 beta:sIL-1Ra cytokine balance in neutrophils in vitro, which might contribute to a lack of endogenous anti-inflammatory signals to dampen inflammation in vivo.