IL-4 decreases the expression of the monocyte differentiation marker CD14, paralleled by an increasing accessory potency

Immunobiology. 1991 Aug;182(5):449-64. doi: 10.1016/S0171-2985(11)80209-3.


IL-4 has been found to affect the phenotype and a variety of functions of human monocytes and macrophages and has been discussed as a monocyte activating protein along with other cytokines, such as IL-1 and IL-6. In this study we compared the effects of the cytokines IL-1, IL-6, IL-4, and a combination of IL-1 and IL-6 on the expression of the CD14 antigen, the FcIIIg receptor molecule CD16 and the MHC-class II molecules HLA-DR and HLA-DP. These molecules represent characteristic monocyte surface markers. Furthermore, the CD14 molecule has been described as a surface antigen of high in vivo relevance representing an indirect receptor for LPS. We further analyzed the effect of IL-4 on monocytes and macrophages with respect to their accessory function to initiate T-lymphocyte proliferation. Human peripheral blood monocytes strongly express the antigen CD14 and maintain it as a stable surface molecule during their differentiation to macrophages. Flow cytometry analysis of cultured monocytes demonstrated that cells incubated in the presence of IL-4, but not IL-1 and/or IL-6 revealed a reduced expression of the CD14 antigen in a dose- and time-dependent manner. After 3 days IL-4 treated cells were virtually CD14-negative. At the same time the expression of the CD16 antigen (FcRIIIg) was also strongly reduced, whereas the treatment with IL-4 led to an increased expression of MHC class II antigens such as HLA-DR and HLA-DP. The spontaneous low expression of HLA-DQ antigen on monocytes was not affected by any of the cytokines. Functionally, IL-4 treated CD14-negative monocytes exhibited a more than 2-fold higher activity to stimulate an accessory cell-dependent T cell proliferation. This was found in a mitogenic assay and in MLC when compared to monocytes cultured in the absence of IL-4. These observations provide further evidence that IL-4 is a major modulator of monocyte surface antigen expression. Moreover, IL-4 has an enhancer-effect on monocytes as accessory cells and therefore may be of considerable importance as a regulatory factor during monocyte development to accessory cells. Inasmuch as the CD14 molecule functions as a receptor for LPS-binding protein, our results suggest that IL-4 might also play an important regulatory role in processes initiated by bacterial lipopolysaccharides during inflammation and sepsis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • Antigens, CD / biosynthesis*
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / biosynthesis*
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • HLA-DP Antigens / biosynthesis
  • HLA-DR Antigens / biosynthesis
  • Humans
  • Interleukin-1 / immunology
  • Interleukin-1 / pharmacology
  • Interleukin-4 / pharmacology*
  • Interleukin-6 / pharmacology
  • Lipopolysaccharide Receptors
  • Lymphocyte Activation
  • Lymphocyte Culture Test, Mixed
  • Macrophages / drug effects
  • Macrophages / immunology
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Receptors, Fc / biosynthesis
  • Receptors, IgG
  • Time Factors
  • Tumor Necrosis Factor-alpha / pharmacology


  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Differentiation, Myelomonocytic
  • HLA-DP Antigens
  • HLA-DR Antigens
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • Receptors, Fc
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor