Cited by 1,012Cytokine Signaling Pathways and InteractionsImmune Response and InflammationT-cell and B-cell Immunology

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Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF

Schindler, R, Mancilla, J, Endres, S, Ghorbani, R, Clark, SC, Dinarello, CA·1990·Blood

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Abstract

Interleukin-6 (IL-6) shares several biologic properties with IL-1, including hematopoietin-1 activity and stimulation of T cells. Because many of their biologic activities overlap, we developed and used a specific radioimmunoassay (RIA) for IL-6 to compare production of this cytokine on a molar basis with that of IL-1 alpha, IL-1 beta, and tumor necrosis factor (TNF)alpha. The RIA correlated well with the hybridoma bioassay for IL-6 (r = .87, P less than .001). Freshly isolated human peripheral blood mononuclear cells (PBMC) cultured in the absence of stimuli did not produce IL-6 in most cases. Kinetics of secretion and cell-association of IL-6 were studied. In contrast to IL-1 alpha but similar to TNF, IL-6 was almost entirely secreted into the extracellular fluid. Incubation with different stimuli (lipopolysaccharide [LPS], phytohemagglutinin [PHA], Staphylococcus epidermidis, or IL-1 alpha) resulted in production of IL-6. However, on a molar basis PBMC produced approximately two to three times less IL-6 than IL-1 alpha, IL-1 beta, or TNF, regardless of the stimulus. The amount of IL-6 produced from PBMC was consistent when measured in the same subjects six time during a 12-week period. In a cohort of 38 donors, the coefficient of variation for IL-6 production was .32, compared with .92 for IL-1 beta and .96 for TNF. Comparing cytokine production by PBMC, there was a significant correlation between IL-6 and IL-1 beta (r = .72) and between IL-6 and TNF (r = .66). IL-6 did not stimulate IL-1 beta or TNF production, but suppressed IL-1 beta and TNF production induced by LPS or PHA by 30% (P less than .01). This suppression of IL-1 beta and TNF by IL-6 appears to be on the level of transcription.

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Crossref · 10.1182/blood.v75.1.40.40

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Authors: Schindler, R., Mancilla, J., Endres, S., Ghorbani, R., Clark, S., & Dinarello, C.
Affiliations: Tufts University (US)
Department of Medicine, Tufts University School of Medicine, Boston, MA.
ORCID: Endres, S
Venue: Blood
Publisher: American Society of Hematology
Published: 1990-01-01
Volume: 75
Issue: 1
Pages: 40-47
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood.v75.1.40.40
OpenAlex: W204546040
Cited by: 1,012
References: 34
Citations by year: 2026: 7 · 2025: 17 · 2024: 16 · 2023: 11 · 2022: 29 · 2021: 19 · 2020: 22 · 2019: 31 · 2018: 33 · 2017: 18 · 2016: 35 · 2015: 17 · 2014: 32 · 2013: 26 · 2012: 38
FWCI: 24.10
Type: journal article
Language: en
Open access: closed
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (AI‑15614)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: interleukin-6, IL-1β, TNF-α, cytokine production, peripheral blood mononuclear cells, cytokine inhibition, lipopolysaccharide, phytohemagglutinin, Staphylococcus epidermidis, radioimmunoassay, transcriptional regulation, hematopoietic function
MeSH terms: Biological Assay, Gene Expression Regulation, Humans, Interleukin-1, Leukocytes, Mononuclear, Radioimmunoassay, RNA, Messenger, Tumor Necrosis Factor-alpha, Interleukin-6, In Vitro Techniques

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Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF

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