Djoba Siawaya J F, Beyers N, van Helden P, Walzl G
Division of Molecular Biology and Human Genetics/MRC Centre for Molecular and Cellular Biology/DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
Clin Exp Immunol. 2009 Apr;156(1):69-77. doi: 10.1111/j.1365-2249.2009.03875.x. Epub 2009 Jan 22.
Biomarkers for treatment response would facilitate the testing of urgently needed new anti-tuberculous drugs. The present study investigated the profiles of 30 proinflammatory, anti-inflammatory and angiogenic factors [epidermal growth factor, eotaxin, fractalkine, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1alpha, IL-1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, interferon-gamma, interferon-inducible protein-10, Krebs von den Lungen-6, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, sCD40L, transforming growth factor-alpha, tumour necrosis factor-alpha and vascular endothelial growth factor] in the plasma of 12 healthy tuberculin skin test-positive community controls and 20 human immunodeficiency virus-negative patients with active tuberculosis (TB) and identified potential biomarkers for early treatment response. We showed differences in the level of circulating cytokines between healthy controls and TB patients, but also between fast responders and slow responders to anti-tuberculosis treatment. The general discriminant analysis based on pre-treatment and week 1 measurements identified 10 sets of three-variable models that could classify fast and slow responders with up to 83% accuracy. Overall, this study shows the potential of cytokines as indicators of anti-tuberculosis treatment response.
治疗反应生物标志物将有助于对急需的新型抗结核药物进行测试。本研究调查了12名健康结核菌素皮肤试验阳性社区对照者和20名人类免疫缺陷病毒阴性的活动性肺结核（TB）患者血浆中30种促炎、抗炎和血管生成因子[表皮生长因子、嗜酸性粒细胞趋化因子、 fractalkine、粒细胞集落刺激因子、粒细胞巨噬细胞集落刺激因子、白细胞介素（IL）-1α、IL-1β、IL-1ra、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12p40、IL-12p70、IL-13、IL-15、IL-17、干扰素-γ、干扰素诱导蛋白-10、Krebs von den Lungen-6、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白（MIP）-1α、MIP-1β、可溶性CD40配体、转化生长因子-α、肿瘤坏死因子-α和血管内皮生长因子]的水平，并确定了早期治疗反应的潜在生物标志物。我们发现健康对照者和TB患者之间以及抗结核治疗的快速反应者和缓慢反应者之间循环细胞因子水平存在差异。基于治疗前和第1周测量的一般判别分析确定了10组三变量模型，这些模型可以以高达83%的准确率对快速和缓慢反应者进行分类。总体而言，本研究显示了细胞因子作为抗结核治疗反应指标的潜力。
