Tuberculosis in poorly controlled type 2 diabetes: Altered cytokine expression in peripheral white blood cells
Tuberculosis in poorly controlled type 2 diabetes: Altered cytokine expression in peripheral white blood cells
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DOI：
10.1086/590565
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发表时间：
2008-09-01
影响因子：
11.8
通讯作者：
McCormick, Joseph B.
中科院分区：
文献类型：
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作者：
Restrepo, Blanca I.;Fisher-Hoch, Susan P.;McCormick, Joseph B.
背景虽然糖尿病患者对结核病易感性增加的生物学基础尚不清楚，但世界正在经历2型糖尿病的大流行。我们假设慢性高血糖导致免疫功能低下，促进进展为活动性结核。为了评估这种可能性，我们确定了结核病和糖尿病患者（特别是慢性高血糖患者）与未患糖尿病的结核病患者相比，是否存在对分枝杆菌抗原的细胞因子应答改变。来自结核病和糖尿病患者以及来自未患有糖尿病的结核病患者的全血样品在体外用来自结核分枝杆菌的纯化蛋白衍生物刺激。然后，我们确定了在控制了可能的混淆因素后，先天性和适应性细胞因子分泌水平与糖尿病状态或糖尿病伴慢性高血糖（通过糖化血红蛋白水平测量）之间是否存在关联。先天性和1型细胞因子的反应显着高于结核病患者谁有糖尿病比非糖尿病对照组。在糖尿病合并慢性高血糖患者中，这种作用持续且显著。这些数据提供了初步证据，表明2型糖尿病，特别是涉及慢性高血糖的2型糖尿病，与对M的免疫应答改变有关。结核对潜在机制的更详细的了解应该集中在慢性高血糖对免疫反应的影响上，以帮助理解糖尿病患者对结核病的易感性增强。
Background. Although the biological basis for the increased susceptibility of diabetic patients to tuberculosis remains unclear, the world is undergoing a type 2 diabetes pandemic. We hypothesize that chronic hyperglycemia leads to immunocompromise that facilitates progression to active tuberculosis. To assess this possibility, we determined whether patients with tuberculosis and diabetes (particularly those with chronic hyperglycemia), compared with patients with tuberculosis who did not have diabetes, presented altered cytokine responses to a mycobacterial antigen.Methods. Samples of whole blood from patients with tuberculosis and diabetes and from patients with tuberculosis who did not have diabetes was stimulated in vitro with purified protein derivative from Mycobacterium tuberculosis. We then determined whether there was an association between the levels of innate and adaptive cytokines secreted in response to the antigen and diabetes status, or diabetes with chronic hyperglycemia (measured by glycosylated hemoglobin level), after controlling for possible confounders.Results. Innate and type 1 cytokine responses were significantly higher in patients with tuberculosis who had diabetes than in nondiabetic control subjects. The effect was consistently and significantly more marked in diabetic patients with chronic hyperglycemia.Conclusions. These data provide preliminary evidence that type 2 diabetes, especially type 2 diabetes involving chronic hyperglycemia, is associated with an altered immune response to M. tuberculosis. More-detailed knowledge of the underlying mechanisms should focus on the effect of chronic hyperglycemia on the immune response to help in understanding the enhanced susceptibility of diabetic patients to tuberculosis.