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Cited by 817Cytokine Signaling Pathways and InteractionsRheumatoid Arthritis Research and TherapiesImmune Response and Inflammation

Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55.

Tilg, H, Trehu, E, Atkins, MB, Dinarello, CA, Mier, JW·1994·Blood
DOI 10.1182/blood.v83.1.113.113
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Abstract

The aim of this study was to investigate whether interleukin (IL)-6 induces the production of IL-1 and tumor necrosis factor (TNF) antagonists. Serial plasma samples were obtained from cancer patients participating in phase I and II trials of recombinant IL-6 administered as a 120-hour continuous intravenous (IV) infusion. Plasma IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor p55 (TNFsRp55) levels were measured by specific radioimmunoassays (RIAs). IL-1Ra levels increased rapidly, reaching peak values (9.6 +/- 1.7 ng/mL) within 2 to 4 hours of beginning treatment. Thereafter, levels promptly declined, reaching near baseline within 24 hours despite continuation of IL-6. TNFsRp55 plasma levels increased within 4 to 8 hours after initiating treatment and increased progressively throughout the duration of therapy. IL-1 beta and TNF-alpha plasma levels were below the detection limit in all samples tested. Peripheral blood mononuclear cells (PBMC) exposed to IL-6 produced only small amounts (1.56 +/- 0.3 ng/mL) of IL-1Ra, even in the presence of exogenous soluble IL-6 receptor (gp80). TNFsRp55 levels measured in the supernatants of IL-6-stimulated PBMC were below the detection limit of the assay. Macrophages generated by culturing monocytes in granulocyte-macrophage colony-stimulating factor (GM-CSF) were much more responsive to IL-6 than freshly isolated unfractionated or adherent PBMC and synthesized almost as much IL-1Ra when stimulated with IL-6 as with endotoxin. These results suggest that the antinflammatory properties of IL-6 may be due; in part, to the induction of IL-1Ra synthesis and the release of soluble TNF receptors. Our findings also suggest that tissue macrophages may be an important source of IL-6-induced IL-1Ra.

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Crossref · 10.1182/blood.v83.1.113.113

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  • IL-1 is extremely unlikely to be an important systemic mediator of HPAA activation during TPS-induced inflammation.

    “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 [41]

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Authors
Tilg, H., Trehu, E., Atkins, M., Dinarello, C., & Mier, J.
Affiliations
  • Tufts Medical Center (US)
  • Department of Medicine, New England Medical Center, Boston, MA 02111.
ORCID
Tilg, H
Venue
Blood
Publisher
American Society of Hematology
Published
1994-01-01
Volume
83
Issue
1
Pages
113-118
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v83.1.113.113
OpenAlex
W95884546
Cited by
817
References
34
Citations by year
2026: 5 · 2025: 4 · 2024: 5 · 2023: 17 · 2022: 17 · 2021: 20 · 2020: 14 · 2019: 29 · 2018: 23 · 2017: 19 · 2016: 29 · 2015: 29 · 2014: 31 · 2013: 31 · 2012: 29
FWCI
11.56
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ca043950-11)
  • National Cancer Institute (UO1 CA 07190, CA-43950)
  • National Institute of Allergy and Infectious Diseases (AI‑15614)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
interleukin-6, interleukin-1 receptor antagonist, anti-inflammatory cytokines, plasma cytokines, peripheral blood mononuclear cells, macrophages, IL-1β, TNF-α, cancer patients
MeSH terms
Anti-Inflammatory Agents, Humans, Leukocytes, Mononuclear, Lipopolysaccharides, Macrophages, Neoplasms, Sialoglycoproteins, Interleukin-6, Granulocyte-Macrophage Colony-Stimulating Factor, Receptors, Tumor Necrosis Factor, Interleukin 1 Receptor Antagonist Protein

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