Taha R A, Minshall E M, Olivenstein R, Ihaku D, Wallaert B, Tsicopoulos A, Tonnel A B, Damia R, Menzies D, Hamid Q A
Meakins-Christie Laboratories and Montreal Chest Research Institute, McGill University, Montreal, Quebec, Canada.
Am J Respir Crit Care Med. 1999 Oct;160(4):1119-23. doi: 10.1164/ajrccm.160.4.9807120.
Cytokines have been implicated in the pathophysiology and development of pulmonary diseases such as tuberculosis and sarcoidosis. In particular, the numbers of cells expressing Th1-type cytokines such as IFN-gamma and IL-12 are increased within the lungs of patients with these granulomatous diseases. As a factor promoting the commitment of naive lymphocytes to a Th1-type profile of cytokine expression, IL-12 may be pivotal in the cascade of proinflammatory events within the airways. In this study, we examined the expression of the IL-12 receptor (IL-12R) mRNA in bronchoalveolar lavage (BAL) fluid from patients with active pulmonary tuberculosis (n = 6) and active pulmonary sarcoidosis (n = 6), and from allergic asthmatics (n = 6) and normal control subjects (n = 6). Bronchoscopy with BAL was undertaken, and cell cytospins were examined using the technique of in situ hybridization. There was a significant increase in the numbers of cells expressing mRNA for both beta(1) and beta(2) subunits of the IL-12R in active pulmonary sarcoidosis (p < 0.02, p < 0.01, respectively) and active pulmonary tuberculosis (p < 0.01, p < 0.005, respectively) compared with normal control subjects. In contrast, the allergic asthmatic patients exhibited a significant decrease in the number of IL-12R mRNA-positive cells (both beta(1) and beta(2) subunits (p < 0.01, p < 0.005, respectively), compared with the normal control subjects. These patients did, however, exhibit a significant increase in IL-4R mRNA, which was not evident in those with either tuberculosis or sarcoidosis when compared with normal subjects (p < 0.05). Colocalization studies demonstrated that CD8+ve cells are a principal site for the expression of IL-12R in tuberculosis. In sarcoidosis, IL-12R was expressed both on CD4+ve and CD8+ve cells. The increased expression of receptors for IL-12 in granulomatous diseases such as pulmonary tuberculosis and sarcoidosis provides evidence supporting the commitment of lymphocytes to a Th1-type cytokine profile in vivo.
细胞因子与诸如肺结核和结节病等肺部疾病的病理生理学及发展有关。特别是，在这些肉芽肿性疾病患者的肺内，表达Th1型细胞因子（如干扰素-γ和白细胞介素-12）的细胞数量会增加。作为促使未成熟淋巴细胞向Th1型细胞因子表达谱分化的一个因素，白细胞介素-12可能在气道内促炎事件的级联反应中起关键作用。在本研究中，我们检测了活动性肺结核患者（n = 6）、活动性结节病患者（n = 6）、过敏性哮喘患者（n = 6）及正常对照者（n = 6）支气管肺泡灌洗（BAL）液中白细胞介素-12受体（IL-12R）mRNA的表达。进行了BAL支气管镜检查，并使用原位杂交技术检查细胞涂片。与正常对照者相比，活动性结节病（分别为p < 0.02，p < 0.01）和活动性肺结核（分别为p < 0.01，p < 0.005）中表达IL-12R β(1)和β(2)亚基mRNA的细胞数量显著增加。相比之下，与正常对照者相比，过敏性哮喘患者IL-12R mRNA阳性细胞数量显著减少（β(1)和β(2)亚基均如此，分别为p < 0.01，p < 0.005）。然而，这些患者IL-4R mRNA显著增加，与正常受试者相比，肺结核或结节病患者中未观察到这种情况（p < 0.05）。共定位研究表明，CD8+阳性细胞是肺结核中IL-12R表达的主要部位。在结节病中，IL-12R在CD4+阳性和CD8+阳性细胞上均有表达。在诸如肺结核和结节病等肉芽肿性疾病中IL-12受体表达增加，这为淋巴细胞在体内向Th1型细胞因子谱分化提供了支持证据。
