Bendtzen K, Morling N, Fomsgaard A, Svenson M, Jakobsen B, Odum N, Svejgaard A
Laboratory of Medical Immunology, Rigshospitalet, Copenhagen N, Denmark.
Scand J Immunol. 1988 Nov;28(5):599-606. doi: 10.1111/j.1365-3083.1988.tb01492.x.
The production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by lipopolysaccharide-activated mononuclear cells from 39 healthy donors was studied in vitro by bioassay and ELISA. The donors were typed for HLA-A, -B, -C, -DR, and -DP antigens. There was no detectable production of TNF beta (lymphotoxin). The intracellular levels of bioactive TNF alpha were minimal or undetectable in all cases. Cells from HLA-DR2+ individuals secreted significantly lower amounts of TNF alpha than cells from HLA-DR2- donors [2 ng/ml (1.5-4.4) and 7.5 ng/ml (3.9-8.3) respectively (medians 25-75%); P less than 0.01]. The difference disappeared if the cells were preactivated for 2 days with 1000 U/ml of recombinant gamma interferon (rIFN-gamma). In some individuals, the TNF alpha response increased considerably after IFN-gamma priming, in particular in those possessing the HLA-DR2 antigen. In contrast, there was no detectable difference in the production of IL-1 beta between the donors, and the IL-1 beta response decreased significantly after rIFN-gamma priming in HLA-DR2+ individuals [2.3 ng/ml (1.1-8.4) versus 7.2 ng/ml (5-7.9); P less than 0.05] and in HLA-DR2- individuals [3 ng/ml (1.1-5.3) versus 5.7 ng/ml (3.9-7.5); P less than 0.01]. There was no correlation between the TNF alpha and IL-1 responses and any of the other HLA-DR, -DP, or -B antigens. There was a significant positive correlation between the levels of TNF alpha measured by ELISA and by cytotoxicity assay. However, the TNF alpha-containing supernatants from 9 out of 37 individuals appeared to contain inhibitor(s) of the biological activity of TNF alpha. The presence of inhibitor(s) was not associated with any HLA antigens.
通过生物测定法和酶联免疫吸附测定法（ELISA）在体外研究了来自39名健康供体的脂多糖激活的单核细胞产生肿瘤坏死因子（TNF）和白细胞介素1（IL-1）的情况。对供体进行了HLA-A、-B、-C、-DR和-DP抗原分型。未检测到TNFβ（淋巴毒素）的产生。在所有情况下，生物活性TNFα的细胞内水平极低或无法检测到。来自HLA-DR2+个体的细胞分泌的TNFα量明显低于来自HLA-DR2-供体的细胞[分别为2 ng/ml（1.5 - 4.4）和7.5 ng/ml（3.9 - 8.3）（中位数25 - 75%）；P < 0.01]。如果用1000 U/ml的重组γ干扰素（rIFN-γ）将细胞预激活2天，这种差异就会消失。在一些个体中，IFN-γ预刺激后TNFα反应显著增加，尤其是那些具有HLA-DR2抗原的个体。相比之下，供体之间IL-1β的产生没有可检测到的差异，但在HLA-DR2+个体中，rIFN-γ预刺激后IL-1β反应显著降低[2.3 ng/ml（1.1 - 8.4）对7.2 ng/ml（5 - 7.9）；P < 0.05]，在HLA-DR2-个体中也是如此[3 ng/ml（1.1 - 5.3）对5.7 ng/ml（3.9 - 7.5）；P < 0.01]。TNFα和IL-1反应与任何其他HLA-DR、-DP或-B抗原之间均无相关性。通过ELISA和细胞毒性测定法测得的TNFα水平之间存在显著正相关。然而，37名个体中有9名个体的含TNFα的上清液似乎含有TNFα生物活性的抑制剂。抑制剂的存在与任何HLA抗原均无关联。
