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.
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.
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
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D'Andrea
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Ma
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Aste-Amezaga
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Paganin
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Trinchieri
D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D018793:Interleukin-13; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4