Association between HLA‐DR2 and Production of Tumour Necrosis Factor α and Interleukin 1 by Mononuclear Cells Activated by Lipopolysaccharide

Abstract

The production of tumour necrosis factor (TNF) and interleukin 1 (IL-1) by lipopolysacharide-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 < 0.01]. The difference disappeared if the cells were preactivated for 2 days with 1000 U/ml or 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 < 0.05] and in HLA-DR2- individuals [3 ng/ml (1.1-5.3) versus 5.7 ng/ml (3.9-7.5); P < 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.