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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.

TitleStimulatory 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.
Publication TypeJournal Article
Year of Publication1995
AuthorsD'Andrea A, Ma X, Aste-Amezaga M, Paganin C, Trinchieri G
JournalJ Exp Med
Volume181
Issue2
Pagination537-46
Date Published1995 Feb 01
ISSN0022-1007
KeywordsAnimals, Cell Line, CHO Cells, Cricetinae, Humans, Interleukin-10, Interleukin-12, Interleukin-13, Interleukin-4, Kinetics, Leukocytes, Mononuclear, Staphylococcus aureus, Transforming Growth Factor beta, Tumor Necrosis Factor-alpha
Abstract

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.

DOI10.1084/jem.181.2.537
Alternate JournalJ Exp Med
PubMed ID7836910
PubMed Central IDPMC2191875
Grant ListCA-10815 / CA / NCI NIH HHS / United States
CA-20833 / CA / NCI NIH HHS / United States
CA-32898 / CA / NCI NIH HHS / United States

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