Thalidomide suppressed IL-1β while enhancing TNF-α and IL-10, when cells in whole blood were stimulated with lipopolysaccharide
Thalidomide suppressed IL-1β while enhancing TNF-α and IL-10, when cells in whole blood were stimulated with lipopolysaccharide
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DOI：
10.1080/08923970802135161
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Kamath, Burde
中科院分区：
文献类型：
--
作者：
Shannon, Edward;Noveck, Robert;Kamath, Burde
沙利度胺用于治疗麻风结节性红斑（ENL）。这种炎症反应可能发生在多菌型麻风患者中，而引起炎症反应的事件以及沙利度胺阻止ENL的机制尚不清楚。沙利度胺在体外抑制肿瘤坏死因子α（TNF-α）的能力被认为是其有效治疗ENL的部分原因。这取决于用于诱发TNF-α的兴奋剂;用于从血液中分离单核细胞的程序，以及培养物中主要的单核细胞类型。为了避免在从血液中分离单核细胞的过程中可能出现的伪影，我们用LPS刺激正常人血液，并评估沙利度胺和地塞米松对TNF-α和其他炎性细胞因子和生物标志物的影响。（IL-1 β）（p = 0.007），并增强TNF-α（p = 0.007）和白细胞介素10（IL-10）（p = 0.031）。地塞米松增强IL-10（p = 0.013），抑制IL-1 β、TNF-α白细胞介素6（IL-6）和白细胞介素8（IL-8）（p = 0.013）。这两种药物不能抑制：C反应蛋白（CRP）、Ig超家族细胞粘附分子1（ICAM 1）、肿瘤坏死因子受体1（TNFR 1）、肿瘤坏死因子受体2（TNFR 2）或淀粉样蛋白A。在体外和体内的证据越来越多，TNF-α是不是主要的细胞因子的沙利度胺在ENL和其他炎症条件下的目标。
Thalidomide is used to treat erythema nodosum leprosum (ENL). The events that precipitate this inflammatory reaction, which may occur in multibacillary leprosy patients, and the mechanism by which thalidomide arrest ENL, are not known. Thalidomide's ability to inhibit tumor necrosis factor alpha (TNF-alpha) in vitro has been proposed as a partial explanation of its effective treatment of ENL.In in vitro assays, thalidomide can enhance or suppress TNF-alpha. This is dependent on the stimulant used to evoke TNF-alpha; the procedure used to isolate the mononuclear cells from blood, and the predominant mononuclear cell type in the culture. To avoid artifacts that may occur during isolation of mononuclear cells from blood, we stimulated normal human blood with LPS and evaluated the effect of thalidomide and dexamethasone on TNF-, and other inflammatory cytokines and biomarkers.Thalidomide suppressed interleukin 1 beta (IL-1 beta) (p = 0.007), and it enhanced TNF-alpha (p = 0.007) and interleukin 10 (IL-10) (p = 0.031). Dexamethasone enhanced IL-10 (p = 0.013) and suppressed IL-1 beta, TNF-alpha interleukin 6 (IL-6), and interleukin 8 (IL-8) (p = 0.013). The two drugs did not suppress: C-reactive protein (CRP), Ig-superfamily cell-adhesion molecule 1 (ICAM 1), tumor necrosis factor receptor 1 (TNFR1), tumor necrosis factor receptor 2 (TNFR2), or amyloid A. In vitro and in vivo evidence is accumulating that TNF-alpha is not the primary cytokine targeted by thalidomide in ENL and other inflammatory conditions.