Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis.
Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis.
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DOI：
10.4049/jimmunol.145.1.149
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发表时间：
1990-07
影响因子：
4.4
通讯作者：
Peter F. Barnes;S. Fong;Patrick J. Brennan;P. Twomey;A. Mazumder;R. Modlin
中科院分区：
文献类型：
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作者：
Peter F. Barnes;S. Fong;Patrick J. Brennan;P. Twomey;A. Mazumder;R. Modlin
TNF和IFN-γ被认为参与对分枝杆菌感染的免疫应答，因为它们在体外表现出抗分枝杆菌作用。为了研究这些细胞因子在人类结核病疾病活动部位的体内作用，我们评估了结核性胸膜炎患者局部细胞因子的产生。与相同患者的血液相比，TNF和IFN-γ在胸腔液中选择性浓缩5至30倍。通过原位杂交在胸膜组织中检测到两种细胞因子的信使RNA，表明选择性细胞因子浓度是由于局部细胞因子产生。结核分枝杆菌细胞壁的两个组成部分，蛋白质-肽聚糖复合物和脂阿拉伯甘露聚糖，引起剂量依赖性释放TNF的胸膜液单核细胞，并可能构成刺激TNF的生产在胸膜腔。与TNF释放的结果相反，蛋白质-肽聚糖复合物，但不是脂阿拉伯甘露聚糖，刺激IFN-γ释放的胸腔液单核细胞。结核性胸膜炎的临床表现，如发热、渗出性胸腔积液和组织坏死，可能是由于局部TNF浓度升高的影响，产生于对分枝杆菌细胞壁成分的反应。
TNF and IFN-gamma are thought to be involved in the immune response to mycobacterial infection because they exhibit antimycobacterial effects in vitro. To investigate the roles of these cytokines in vivo at the site of disease activity in human tuberculosis, we evaluated local cytokine production in patients with tuberculous pleuritis. Both TNF and IFN-gamma were selectively concentrated 5- to 30-fold in pleural fluid, compared to blood of the same patients. Messenger RNA for both cytokines was detected in pleural tissue by in situ hybridization, suggesting that selective cytokine concentration is due to local cytokine production. Two Mycobacterium tuberculosis cell wall components, the protein-peptidoglycan complex and lipoarabinomannan, caused dose-dependent release of TNF by pleural fluid mononuclear cells and may constitute the stimuli for TNF production in the pleural space. In contrast to results obtained for TNF release, the protein-peptidoglycan complex, but not lipoarabinomannan, stimulated IFN-gamma release by pleural fluid mononuclear cells. The clinical manifestations of tuberculous pleuritis, such as fever, exudative pleural effusion, and tissue necrosis, may be due to the effects of elevated local TNF concentrations, produced in response to mycobacterial cell wall components.