Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease
Thalidomide attenuates excessive inflammation without interrupting lipopolysaccharide-driven inflammatory cytokine production in chronic granulomatous disease
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DOI：
10.1016/j.clim.2013.03.004
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发表时间：
2013-05-01
影响因子：
8.6
通讯作者：
Onodera, Masafumi
中科院分区：
文献类型：
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作者：
Kawai, Toshinao;Watanabe, Nobuyuki;Onodera, Masafumi
慢性肉芽肿病(CGD)是一种罕见的遗传性疾病，其特征是无法产生活性氧物种，导致反复发生威胁生命的感染。奇怪的是，一半的CGD患者患有无菌性肠炎(CGD结肠炎)，这是由于TNF-α和IL-1β引起的炎症调节失调。因此，开发在不中断抗微生物免疫的情况下调节过度炎症反应的治疗方法将使CGD结肠炎患者受益。在这里，我们发现沙利度胺抑制了肿瘤坏死因子-α诱导的核因子-kappaB的激活和三磷酸腺苷诱导的IL-1β的分泌，但不阻断脂多糖对CGD单核细胞产生IL-1β、IL-6、IL-8和TNF-α的反应。我们报告了一例CGD结肠炎患者，在沙利度胺治疗开始时，表现为肠道炎症减轻，特征是血清炎性细胞因子水平降低，但没有出现真菌和细菌感染进展的证据。我们的结果提示，沙利度胺可能是治疗CGD结肠炎合并严重感染的有效选择。(C)2013 Elsevier Inc.保留所有权利。
Chronic granulomatous disease (CGD) is a rare inherited disorder characterized by an inability to produce reactive oxygen species, resulting in recurrent life-threatening infections. Curiously, half of the patients with CGD suffer from aseptic bowel inflammation (CGD colitis) due to dysregulated inflammation induced by TNF-alpha and IL-1 beta. Thus, developing therapies that regulate excessive inflammatory responses without interrupting antimicrobial immunity would benefit CGD colitis patients. Here, we show that thalidomide suppressed TNF-alpha-induced NF-kappa B activation and ATP-induced IL-1 beta secretion, but did not interrupt the production of IL-1 beta, IL-6, IL-8, and TNF-alpha in response to lipopolysaccharide in CGD monocytes. We report on a CGD colitis patient that showed decreased bowel inflammation characterized by reduced serum levels of inflammatory cytokines without evidence of progression of fungal and bacterial infections present at initiation of thalidomide therapy. Our results suggest that thalidomide could be an efficacious therapeutic option for patients with CGD colitis suffering from serious infections. (C) 2013 Elsevier Inc. All rights reserved.