Cited by 3,762Cytokine Signaling Pathways and InteractionsImmune Response and InflammationImmune cells in cancer

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Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.

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de Waal Malefyt, R, Abrams, J, Bennett, B, Figdor, C G, de Vries, J E·1991·The Journal of experimental medicine

DOI 10.1084/jem.174.5.1209PMC PMC2119001

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Abstract

In the present study we demonstrate that human monocytes activated by lipopolysaccharides (LPS) were able to produce high levels of interleukin 10 (IL-10), previously designated cytokine synthesis inhibitory factor (CSIF), in a dose dependent fashion. IL-10 was detectable 7 h after activation of the monocytes and maximal levels of IL-10 production were observed after 24-48 h. These kinetics indicated that the production of IL-10 by human monocytes was relatively late as compared to the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, tumor necrosis factor alpha (TNF alpha), and granulocyte colony-stimulating factor (G-CSF), which were all secreted at high levels 4-8 h after activation. The production of IL-10 by LPS activated monocytes was, similar to that of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF, inhibited by IL-4. Furthermore we demonstrate here that IL-10, added to monocytes, activated by interferon gamma (IFN-gamma), LPS, or combinations of LPS and IFN-gamma at the onset of the cultures, strongly inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF at the transcriptional level. Viral-IL-10, which has similar biological activities on human cells, also inhibited the production of TNF alpha and GM-CSF by monocytes following LPS activation. Activation of monocytes by LPS in the presence of neutralizing anti-IL-10 monoclonal antibodies resulted in the production of higher amounts of cytokines relative to LPS treatment alone, indicating that endogenously produced IL-10 inhibited the production of IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF alpha, GM-CSF, and G-CSF. In addition, IL-10 had autoregulatory effects since it strongly inhibited IL-10 mRNA synthesis in LPS activated monocytes. Furthermore, endogenously produced IL-10 was found to be responsible for the reduction in class II major histocompatibility complex (MHC) expression following activation of monocytes with LPS. Taken together our results indicate that IL-10 has important regulatory effects on immunological and inflammatory responses because of its capacity to downregulate class II MHC expression and to inhibit the production of proinflammatory cytokines by monocytes.

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Background
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Authors: de Waal Malefyt, R., Abrams, J., Bennett, B., Figdor, C. G., & de Vries, J. E.
Affiliations: Department of Human Immunology, DNAX Research Institute, Palo Alto, California 94304.
ORCID: Figdor, C G
Venue: The Journal of experimental medicine
Publisher: Rockefeller University Press
Published: 1991-11-01
Volume: 174
Issue: 5
Pages: 1209-1220
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.174.5.1209
PMC: PMC2119001
OpenAlex: W2191654227
Cited by: 3,762
References: 41
Citations by year: 2026: 25 · 2025: 41 · 2024: 45 · 2023: 60 · 2022: 58 · 2021: 68 · 2020: 67 · 2019: 80 · 2018: 69 · 2017: 71 · 2016: 97 · 2015: 98 · 2014: 132 · 2013: 107 · 2012: 122
FWCI: 39.70
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: cc-by-nc-sa
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion, other-oa)
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 › Immune cells in cancer
Keywords: IL-10, monocytes, cytokine synthesis inhibition, lipopolysaccharide stimulation, interferon-gamma, autoregulation, cytokine gene expression, MHC class II expression, viral IL-10, TNF-α, GM-CSF, granulocyte colony-stimulating factor, interleukin-6, interleukin-8
MeSH terms: Histocompatibility Antigens Class II, Base Sequence, Cells, Cultured, Homeostasis, Humans, Interferon-gamma, Interleukin-1, Lipopolysaccharides, Molecular Sequence Data, Monocytes, RNA, Messenger, Transcription, Genetic, Interleukin-4, Interleukin-6, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Transforming Growth Factor beta, Interleukin-10

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Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.

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