Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: priming for IL-12 and tumor necrosis factor alpha production
Open accessAbstract
The production of cytokines in monocytes/macrophages is regulated by several different cytokines that have activating or inhibitory effects. Interleukin (IL)-10, IL-4, IL-13, and transforming growth factor (TGF)-beta are usually considered to be the most important macrophage-deactivating factors, with inhibitory effects on cytokine production. Unlike IL-10 and TGF-beta, which appear to act as downmodulators of many phagocytic cell functions, the mode of action of IL-4 and IL-13 is more complex. Addition of IL-4 and IL-13 to peripheral blood mononuclear cell (PBMC) cultures inhibited production of IL-12, tumor necrosis factor (TNF)-alpha, IL-10, and IL-1 beta induced by lipopolysaccharide (LPS) or Staphylococcus aureus added simultaneously with the cytokines. However, pretreatment of PBMC with IL-4 or IL-13 for > or = 20 h enhanced the production of IL-12 and TNF-alpha in response to LPS or S. aureus several fold in these cells; this IL-4-induced priming for the two cytokines was inhibited by anti-IL-4 neutralizing antibodies. IL-4 priming also enhanced the accumulation of IL-12 and TNF-alpha mRNA induced by LPS and S. aureus. The enhanced accumulation of transcripts for the IL-12 p35 and p40 chains by IL-4 priming was reflected in enhanced secretion of both the IL-12 free p40 chain and the p70 heterodimer. These results suggest an unexpected complexity in the regulatory role of IL-4 and IL-13 in immune responses.
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The induction of TNF-a and IL-12 production by LPS can be significantly dampened in the presence of IL-4.
“for example, the induction of TNF-a and IL-12 production by the pro-inflammatory (M1 polarizing) cytokine, LPS, can be significantly dampened in the presence of IL-4; a M2 polarizing cytokine produced by nearby M2 macrophages, basophils and mast cells [26].”
From Biomaterial based modulation of macrophage polarization: a review and suggested design principles (2015) · cites this paper as [26]
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References 55 · Cited by 365
- Authors
- D'Andrea, A., Ma, X., Aste-Amezaga, M., Paganin, C., & Trinchieri, G.
- Affiliations
- Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
- The Wistar Institute (US)
- Venue
- The Journal of experimental medicine
- Publisher
- Rockefeller University Press
- Published
- 1995-02-01
- Volume
- 181
- Issue
- 2
- Pages
- 537-546
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2191875
- OpenAlex
- W2145677005
- Cited by
- 365
- References
- 55
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 7 · 2016: 3 · 2015: 6 · 2014: 12 · 2013: 8 · 2012: 13
- FWCI
- 14.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca032898-13, 10815)
- National Cancer Institute (CA 32898, CA-20833, CA-10815, P30CA010815)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- IL-4, IL-13, IL-12, TNF-α, peripheral blood mononuclear cells, macrophage activation, cytokine priming, lipopolysaccharide, Staphylococcus aureus, IL-10, TGF-beta, mRNA accumulation, cytokine regulation
- MeSH terms
- Animals, Cell Line, Cricetinae, Humans, Kinetics, Leukocytes, Mononuclear, Staphylococcus aureus, Tumor Necrosis Factor-alpha, Interleukin-4, Transforming Growth Factor beta, CHO Cells, Interleukin-10, Interleukin-12, Interleukin-13
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