Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes
Interleukin 10 (IL-10) regulation of tumour necrosis factor alpha (TNF-alpha) from human alveolar macrophages and peripheral blood monocytes
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DOI：
10.1136/thx.51.2.143
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发表时间：
1996-02-01
期刊：
影响因子：
10
通讯作者：
Millar, A
中科院分区：
文献类型：
--
作者：
Armstrong, L;Jordan, N;Millar, A
背景-调节人肺内的炎症反应对于防止正常宿主防御反应的这一重要部分成为病理过程至关重要。肿瘤坏死因子-α是一种细胞因子，参与了休克、肉芽肿形成、组织坏死和包括肺在内的许多器官系统的纤维化。白介素10(IL-10)对包括肿瘤坏死因子-α在内的多种炎性细胞因子的产生具有抑制作用。用双抗体夹心酶联免疫吸附试验检测IL-10对肿瘤坏死因子-α蛋白产生的影响，而用肿瘤坏死因子-α特异性寡核苷酸探针通过Northern印迹法检测肿瘤坏死因子-α的mRNA表达。结果：100U/mlIL-10可使肺泡巨噬细胞脂多糖介导的肿瘤坏死因子-α的产生由3.508(0.629)ng/ml降至2.035(0.385)ng/ml。外周血单核细胞产生的肿瘤坏死因子-α由2.035(0.284)ng/ml降至0.698(0.167)ng/ml，肺泡巨噬细胞和外周血单核细胞的肿瘤坏死因子-α基因表达均受到抑制，IL-10可使内毒素诱导的肿瘤坏死因子-α基因表达分别减少47.8(15.2)%和83.1(4.2)%。环己胺对IL-10介导的肿瘤坏死因子-α的抑制作用无明显影响，提示肿瘤坏死因子-α的抑制不需要从头合成蛋白质。结论IL-10可有效抑制肺泡巨噬细胞和外周血单核细胞表达和释放肿瘤坏死因子-α，在肺免疫反应的细胞因子网络中可能起重要作用。
Background - Regulation of the inflammatory response within the human lung is essential to prevent this important part of the normal host defence response becoming a pathological process. Tumour necrosis factor at (TNF-alpha) is a cytokine involved in the pathogenesis of shock and in granuloma formation, tissue necrosis, and fibrosis in many organ systems including the lung. Interleukin 10 (IL-10) has been proposed as having an inhibitory effect on the production of several inflammatory cytokines including TNF-alpha.Methods - The effect of IL-10 administration on TNF-alpha production was explored in human alveolar macrophages and peripheral blood monocytes from matched individuals. The effects of IL-10 on TNF-alpha protein production were determined by sandwich enzyme linked immunosorbant assay (ELISA), whereas the TNF-alpha mRNA response was established by Northern blotting using a TNF-alpha specific oligonucleotide probe. The protein synthesis inhibitors actinomycin D and cyclohexamide were utilised to monitor IL-10 effects on mRNA degradation and de novo protein synthesis, respectively.Results - The lipopolysaccharidee-mediated TNF-alpha production in alveolar macrophages was reduced from 3.508 (0.629) to 2.035 (0.385) ng/ml by 100 U/ml IL-10. Lipopolysaccharide-induced TNF-alpha production in peripheral blood monocytes was reduced from 2.035 (0.284) to 0.698 (0.167) ng/ml. TNF-alpha gene expression was also inhibited in both alveolar macrophages and peripheral blood monocytes; lipopolysaccharide-induced TNF-alpha mRNA was reduced by 47.8 (15.2)% and 83.1 (4.2)%, respectively, by IL-10. The IL-10 mediated suppression of TNF-alpha mRNA was unaffected by addition of cyclohexamide, suggesting that de novo protein synthesis was not required for TNF-alpha inhibition. mRNA stability experiments indicated no acceleration in lipopolysaccharide-induced TNF-alpha mRNA degradation in response to IL-10.Conclusions - These findings suggest that IL-10 is a potent inhibitor of TNF-alpha expression and release from alveolar macrophages and peripheral blood monocytes, and thus it may have an important role in the cytokine network of the pulmonary immune response.