Serum Levels of Interleukin-12 and Interferon Gamma in Pediatric Tuberculosis: A Clinico-Microbiological Correlation

N. Gupta, B. Kashyap, P. Dewan, Puneeta Hyanki
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Abstract

Objective: The interleukin-12/interferon-γ (IL-12/IFN-γ) pathway is the most validated cytokine pathway regulating Mycobacterium tuberculosis infection. The role of IL-12/IFN-γ axis in protecting against tuberculosis (TB) is exhibited in people having mutations in genes encoding these cytokines. We aimed to study the serum levels of IL-12 and IFN-γ in pediatric tuberculosis and their correlation with clinical and microbiological features. Material and Methods: A case-control study was conducted on 60 microbiologically confirmed (smear and/or culture and/or cartridge-based nucleic acid amplification test) or clinically diagnosed (based on clinical features and radiography and/or contact history and/or Mantoux test with/without microbiological confirmation) pediatric TB patients ≤12 years. Serum interleukin-12 and interferon-gamma levels were estimated using enzyme-linked immunosorbent assays.Thirty age- and sex-matched controls were also included in the study. Results: The median IL-12 levels were lower in our pediatric TB patients (488.1 pg/ml) compared to controls (784.8 pg/ml). However, the IFN-γ/IL-12 ratios were significantly higher among the TB patients as compared to the controls. Moreover, the levels of interleukin-12 and interferon gamma were significantly lower in cases with no evidence of TB on chest radiography. IL-12 was significantly lower in patients with hydrocephalus and enlarged ventricles. Higher levels of IL-12 and IFN-γ were associated with positive results by conventional microbiological techniques. Conclusion: The serum IFN-γ level and the IFN-γ/IL-12 ratio were significantly higher in children with TB compared to the controls in this study. Higher IL-12 and IFN-γ levels as well as IFN-γ/IL-12 ratios were associated with positive results by conventional microbiological techniques. Further studies on larger sample sizes could help evaluate the usefulness of interleukin-12 and interferon-γ as potential markers of severity and prognosis in pediatric TB. 
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儿童结核患者血清白细胞介素-12和干扰素γ水平:临床微生物学相关性
目的:白细胞介素-12/干扰素-γ(IL-12/IFN-γ)途径是最有效的调节结核分枝杆菌感染的细胞因子途径。IL-12/IFN-γ轴在预防结核病(TB)中的作用表现在编码这些细胞因子的基因发生突变的人身上。我们旨在研究儿童结核病患者血清IL-12和IFN-γ水平及其与临床和微生物学特征的相关性。材料和方法:对60名≤12岁的经微生物学证实(涂片和/或培养和/或卡式核酸扩增试验)或临床诊断(基于临床特征和放射学和/或接触史和/或Mantoux试验,有/无微生物证实)的儿童结核病患者进行病例对照研究。血清白细胞介素-12和干扰素γ水平采用酶联免疫吸附测定法进行评估。30名年龄和性别匹配的对照也被纳入研究。结果:与对照组(784.8 pg/ml)相比,我们的儿科结核病患者的中位IL-12水平(488.1 pg/ml)较低。然而,与对照组相比,结核病患者的IFN-γ/IL-12比值显著较高。此外,在胸部放射检查中没有结核病证据的病例中,白细胞介素-12和干扰素γ的水平显著降低。IL-12在脑积水和脑室扩大的患者中显著降低。通过常规微生物学技术,较高水平的IL-12和IFN-γ与阳性结果相关。结论:结核病患儿血清IFN-γ水平及IFN-γ/IL-12比值明显高于对照组。通过常规微生物学技术,较高的IL-12和IFN-γ水平以及IFN-γ/IL-12比率与阳性结果相关。对更大样本量的进一步研究有助于评估白细胞介素-12和干扰素-γ作为儿童结核病严重程度和预后的潜在标志物的有用性。
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