Dheda Keertan, Chang Jung-Su, Breen Ronan A M, Kim Louise U, Haddock Jamanda A, Huggett Jim F, Johnson Margaret A, Rook Graham A W, Zumla Alimuddin
Centre for Infectious Diseases and International Health, Royal Free and University College Medical School, 46 Cleveland Street, London W1T 4JF, United Kingdom.
Am J Respir Crit Care Med. 2005 Aug 15;172(4):501-8. doi: 10.1164/rccm.200502-278OC. Epub 2005 May 18.
Tuberculosis progresses despite potent Th1 responses. A putative explanation is the simultaneous presence of a subversive Th2 response. However, interpretation is confounded by interleukin 4delta2 (IL-4delta2), a splice variant and inhibitor of IL-4.
To study levels of mRNA encoding IL-4 and IL-4delta2, and their relationship to treatment and clinical parameters, in cells from lung lavage and blood from patients with pulmonary tuberculosis.
IL-4delta2, IFN-gamma, IL-4, and soluble CD30 (sCD30) levels were measured by polymerase chain reaction and relevant immunoassays in 29 patients and matched control subjects lacking responses to tuberculosis-specific antigens.
mRNA levels for IL-4 and IL-4delta2 were elevated in unstimulated cells from blood and lung lavage of patients versus control subjects (p < 0.005). In control subjects, there were low basal levels of IL-4 and IL-4delta2 mRNA expressed mainly by non-T cells (p < 0.05). However, in patients, there were greater levels of mRNA for both cytokines in both T- and non-T-cell populations (p < 0.05 compared with control subjects). Radiologic disease correlated with the IL-4/IFN-gamma ratio and sCD30 (p < 0.005). After chemotherapy, IL-4 mRNA levels remained unchanged, whereas IL-4delta2 increased in parallel with IFN-gamma (p < 0.05). Sonicates of Mycobacterium tuberculosis upregulated expression of IL-4 relative to IL-4delta2 in mononuclear cell cultures from patients (p < 0.05).
A Th2-like response, prominent in T cells and driven by tuberculosis antigen, is present in tuberculosis and modulated by treatment, suggesting a role for IL-4 and IL-4delta2 in the pathogenesis of tuberculosis and their ratio as a possible marker of disease activity. The specific antigens inducing the IL-4 response require identification to facilitate future vaccine development strategies.
尽管有强大的Th1反应，结核病仍会进展。一种推测的解释是同时存在颠覆性的Th2反应。然而，白细胞介素4δ2（IL-4δ2），一种IL-4的剪接变体和抑制剂，使这种解释变得复杂。
研究肺结核患者肺灌洗细胞和血液中编码IL-4和IL-4δ2的mRNA水平，及其与治疗和临床参数的关系。
通过聚合酶链反应和相关免疫测定法，测量了29例患者以及对结核特异性抗原无反应的匹配对照受试者的IL-4δ2、干扰素-γ（IFN-γ）、IL-4和可溶性CD30（sCD30）水平。
与对照受试者相比，患者血液和肺灌洗未刺激细胞中IL-4和IL-4δ2的mRNA水平升高（p < 0.005）。在对照受试者中，IL-4和IL-4δ2 mRNA的基础水平较低，主要由非T细胞表达（p < 0.05）。然而，在患者中，T细胞和非T细胞群体中两种细胞因子的mRNA水平都更高（与对照受试者相比，p < 0.05）。放射学疾病与IL-4/IFN-γ比值和sCD30相关（p < 0.005）。化疗后，IL-4 mRNA水平保持不变，而IL-4δ2与IFN-γ平行升高（p < 0.05）。结核分枝杆菌超声裂解物相对于患者单核细胞培养物中的IL-4δ2上调了IL-4的表达（p < 0.05）。
在结核病中存在一种类似Th2的反应，在T细胞中突出且由结核抗原驱动，并受治疗调节，这表明IL-4和IL-4δ2在结核病发病机制中起作用，且它们的比值可能是疾病活动的一个标志物。诱导IL-4反应的特异性抗原需要鉴定，以促进未来疫苗开发策略。
