Interleukin-4 regulation of human monocyte and macrophage interleukin-10 and interleukin-12 production. Role of a functional interleukin-2 receptor gamma-chain

Immunology. 1999 Apr;96(4):529-36. doi: 10.1046/j.1365-2567.1999.00711.x.


Interleukin-4 (IL-4) is the prototypic type 2 immunoregulatory cytokine that can suppress the production of many monocyte and macrophage pro-inflammatory mediators. In this study we investigated the regulation by IL-4 of IL-12 and IL-10 production. While IL-4 suppressed lipopolysaccharide (LPS)-induced IL-12 and IL-10 production by human peripheral blood monocytes, IL-4 suppressed LPS-induced IL-12, but not IL-10, production by synovial fluid mononuclear cells from patients with rheumatoid arthritis. IL-4 also suppressed IL-12, but not IL-10 production, by LPS-stimulated in vitro monocyte-derived macrophages. Similarly, IL-4 cannot suppress LPS-induced tumour necrosis factor-alpha (TNF-alpha) production by synovial fluid cells and monocyte-derived macrophages. The failure of IL-4 to regulate IL-10 production is not due to the failure of IL-4 to suppress TNF-alpha, and vice versa. The data suggest that the IL-4 receptor subunit, gammac, is essential for IL-4 regulation of LPS-induced IL-10 production and that a correlation exists between duration of monocyte culture, reduction in gammac mRNA in cultured cells and hyporesponsiveness of monocyte-derived macrophages to IL-4 for regulation of LPS-induced IL-10 production. This study highlights the importance of investigating responses to IL-4, as a potential therapeutic anti-inflammatory agent, by cells isolated from inflammatory sites and not by the more easily accessible blood monocytes. This study emphasizes the involvement of signalling from gammac in IL-4 regulation of LPS-induced IL-10 production by monocytes and macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Cell Culture Techniques
  • Gene Expression Regulation / immunology
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-12 / biosynthesis
  • Interleukin-4 / immunology*
  • Macrophages / immunology*
  • Monocytes / immunology*
  • RNA, Messenger / genetics
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-10
  • Receptors, Interleukin-2 / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Fluid / immunology
  • Tumor Necrosis Factor-alpha / immunology


  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4