Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes.
Open accessAbstract
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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IL-10 suppresses production of pro-inflammatory cytokines such as TNF.
“IL-10 inhibits production of pro-inflammatory cytokines, such as TNF127.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [127]
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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
- 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
- Health Sciences › Medicine › Oncology › 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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