The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
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
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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In the citing paper
“On the other hand, IL-6 has been shown to inhibit the transcription of IL-1 and TNF-α [74] while stimulating the release of IL-1Ra, IL-10, and cortisol in human mononuclear cells [72] (2a).”
In the citing paper
“Previous studies in cultured human monocytes have shown that IL‐6 prevents endotoxin-induced TNF‐α production (213).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [213]
In the citing paper
“Increased IL-1 in IL-6 Ϫ/Ϫ mice is consistent with data indicating that IL-6 plays an important negative regulatory role in IL-1 induction (40,41) and, together with the absence of an increase in circulating IL-6 in IL-1 Ϫ/Ϫ mice, further indicates that IL-1 is extremely unlikely to be an important systemic mediator of HPAA activation.”
From Interleukin-6 is an afferent signal to the hypothalamo-pituitary-adrenal axis during local inflammation in mice (2003) · cites this paper as [40]
In the citing paper
“IL-6 inhibits lipopolysaccharide (LPS)-induced TNF-α production both in cultured human monocytes and in the human monocytic line U937 [66]”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [66]
Citations
Cites
Gauldie, J., Richards, C. D., Harnish, D. C., Lansdorp, P. M., & Baumann, H. J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.20.7251 · Cited by 1,635
Production of hybridoma growth factor by human monocytes
Aarden, L. A., de Groot, E. R., Schaap, O. L., & Lansdorp, P. M. (1987) · European Journal of Immunology · doi:10.1002/eji.1830171004 · Cited by 1,091
Muraguchi, A., Hirano, T., Tang, B., Matsuda, T., Horii, Y., Nakajima, K., & Kishimoto, T. (1988) · The Journal of experimental medicine · doi:10.1084/jem.167.2.332 · Cited by 783
Damme, J. V., Opdenakker, G., Simpson, R. J., Rubira, M. R., Cayphas, S., Vink, A., Billiau, A., & Snick, J. V. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.165.3.914 · Cited by 669
Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression.
Perlmutter, D. H., Dinarello, C. A., Punsal, P. I., & Colten, H. R. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112721 · Cited by 566
Dinarello, C. A., Ikejima, T., Warner, S. J. C., Orencole, S. F., Lonnemann, G., Cannon, J. G., & Libby, P. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.139.6.1902 · Cited by 537
Zilberstein, A., Ruggieri, R., Korn, J. H., & Revel, M. (1986) · The EMBO Journal · doi:10.1002/j.1460-2075.1986.tb04531.x · Cited by 486
SERUM LEVELS OF INTERLEUKIN-6 AND ACUTE PHASE RESPONSES
Nijsten, M. W., de Groot, E. R., ten Duis, H. J., Klasen, H. J., Hack, C. E., & Aarden, L. A. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91413-9 · Cited by 457
Interleukin 6 is involved in interleukin 1‐induced activities
Helle, M., Brakenhoff, J. P. J., de Groot, E. R., & Aarden, L. A. (1988) · European Journal of Immunology · doi:10.1002/eji.1830180619 · Cited by 409
Induction of rat acute‐phase proteins by interleukin 6 in vivo
Geiger, T. M., Andus, T., Klapproth, J., Hirano, T., Kishimoto, T., & Heinrich, P. C. (1988) · European Journal of Immunology · doi:10.1002/eji.1830180510 · Cited by 401
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Sorted by citations
The anti-inflammatory effect of exercise
Petersen, A. M. W., & Pedersen, B. K. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00164.2004 · Cited by 3,100
Muscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388
Interleukin-1 and interleukin-1 antagonism
Dinarello, C. A. (1991) · Blood · doi:10.1182/blood.v77.8.1627.1627 · Cited by 2,292
The Immunomodulatory and Anti-Inflammatory Role of Polyphenols
Yahfoufi, N., Alsadi, N., Jambi, M., & Matar, C. (2018) · Nutrients · doi:10.3390/nu10111618 · Cited by 1,737
Metadata
- 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
- 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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