Diminished Systemic and Antigen-Specific Type 1, Type 17, and Other Proinflammatory Cytokines in Diabetic and Prediabetic Individuals With Latent Mycobacterium tuberculosis Infection
Diminished Systemic and Antigen-Specific Type 1, Type 17, and Other Proinflammatory Cytokines in Diabetic and Prediabetic Individuals With Latent Mycobacterium tuberculosis Infection
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DOI：
10.1093/infdis/jiu329
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发表时间：
2014-11-15
影响因子：
6.4
通讯作者：
Babu, Subash
中科院分区：
文献类型：
--
作者：
Kumar, Nathella Pavan;George, Parakkal Jovvian;Babu, Subash
背景资料。已知2型糖尿病(DM)是活动性肺结核发生的主要危险因素，但其对结核分枝杆菌潜伏感染(下称“潜伏感染”)的影响尚不清楚。我们检测了糖尿病潜伏感染或糖尿病前期(即中度高血糖)患者的循环血浆细胞因子水平，并将其与潜伏感染患者和正常血糖控制患者的水平进行了比较。在糖尿病或糖尿病前期患者中，潜伏感染的特征是循环中1型(干扰素、白介素2和肿瘤坏死因子α)和17型(白介素17F)细胞因子水平降低。这与全身其他致炎细胞因子(白介素1β和白介素18)和抗炎细胞因子白介素10水平下降有关，但与全身2型细胞因子水平下降无关。此外，当检测抗原刺激的全血时，潜伏感染的糖尿病患者的自发水平和结核分枝杆菌抗原特异性的1型和17型细胞因子水平降低。最后，所测量的任何细胞因子水平(白介素22除外)与血红蛋白A1c水平之间没有显著的相关性。我们的数据显示，在存在糖尿病或糖尿病前期的情况下，潜伏感染的特征是细胞因子的产生减少，这与控制结核分枝杆菌的激活有关，这可能是一种潜在的免疫机制，可以解释潜伏感染的糖尿病患者活动性结核病风险的增加。
Background. Diabetes mellitus type 2 (DM) is known to be a major risk factor for the development of active tuberculosis, although its influence on latent Mycobacterium tuberculosis infection (hereafter, "latent infection") remains poorly characterized.Methods. We examined circulating plasma cytokine levels in individuals with latent infection with DM or pre-DM (ie, intermediate hyperglycemia) and compared them to levels in patients with latent infection and normal glycemic control.Results. In persons with DM or pre-DM, latent infection is characterized by diminished circulating levels of type 1 (interferon., interleukin 2, and tumor necrosis factor alpha) and type 17 (interleukin 17F) cytokines. This was associated with decreased systemic levels of other proinflammatory cytokines (interleukin 1 beta and interleukin 18) and the antiinflammatory cytokine interleukin 10 but not with decreased systemic levels of type 2 cytokines. Moreover, latently infected individuals with DM had diminished levels of spontaneous and M. tuberculosis antigen-specific levels of type 1 and type 17 cytokines when antigen-stimulated whole blood was examined. Finally, there was no significant correlation between the levels of any of the cytokines measured (with the exception of interleukin 22) with hemoglobin A1c levels.Conclusions. Our data reveal that latent infection in the presence of DM or pre-DM, is characterized by diminished production of cytokines, implicated in the control of M. tuberculosis activation, allowing for a potential immunological mechanism that could account for the increased risk of active tuberculosis in latently infected individuals with DM.