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Association between HLA‐DR2 and Production of Tumour Necrosis Factor α and Interleukin 1 by Mononuclear Cells Activated by Lipopolysaccharide
Author(s) -
BENDTZEN K.,
MORLING N.,
FOMSGAARD A.,
SVENSON M.,
JAKOBSEN B.,
ØDUM N.,
SVEJGAARD A.
Publication year - 1988
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1988.tb01492.x
Subject(s) - tumor necrosis factor alpha , peripheral blood mononuclear cell , lipopolysaccharide , antigen , lymphotoxin , immunology , priming (agriculture) , cytokine , interleukin , interferon gamma , medicine , in vitro , microbiology and biotechnology , biology , biochemistry , botany , germination
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 TNFβ (lymphotoxin). The intracellular levels of bioactive TNFα were minimal or undetectable in all cases. Cells from HLA‐DR2 + individuals secreted significantly lower amounts of TNFα 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 of recombinant gamma interferon (rIFN‐γ). In some individuals, the TNFα response increased considerably after IFN‐γ priming, in particular in those possessing the HLA‐DR2 antigen. In contrast, there was no detectable difference in the production of IL‐1β between the donors, and the IL‐1β response decreased significantly after rIFN‐γ 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 TNFα 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 TNFα measured by ELISA and by cytotoxicity assay. However, the TNFα‐containing supernatants from 9 out of 37 individuals appeared to contain inhibitor(s) of the biological activity of TNFα. The presence of inhibitor(s) was not associated with any HLA antigens.