Induction of interleukin-12 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid, deviates CD4+ T cells from a Th2 to a Th1 response

Immunology. 2003 Jul;109(3):407-14. doi: 10.1046/j.1365-2567.2003.01673.x.


In this study we investigated whether berberine-mediated induction of interleukin-12 (IL-12) production in antigen-presenting cells could regulate a cytokine profile of antigen-primed CD4+ T helper (Th) cells. Pretreatment with berberine induced IL-12 production in both macrophages and dendritic cells, and significantly increased the levels of IL-12 production in lipopolysaccharide-stimulated macrophages and in CD40 ligand-stimulated dendritic cells. Importantly, berberine pretreatment of macrophages increased their ability to induce interferon-gamma (IFN-gamma) and reduced their ability to induce IL-4 in antigen-primed CD4+ T cells. Berberine did not influence the macrophage cell surface expression of the class II major histocompatibility complex molecule, the co-stimulatory molecules CD80 and CD86, and intracellular adhesion molecule-1. Addition of neutralizing anti-IL-12p40 monoclonal antibody to cultures of berberine-pretreated macrophages and CD4+ T cells restored IL-4 production in antigen-primed CD4+ T cells. The in vivo administration of berberine resulted in the enhanced induction of IL-12 production by macrophages when stimulated in vitro with lipopolysaccharide or heat-killed Listeria monocytogenes, leading to the inhibition of the Th type 2 cytokine profile (decreased IL-4 and increased IFN-gamma production) in antigen-primed CD4+ T cells. These findings may point to a possible therapeutic use of berberine or medicinal plants containing berberine in the Th type 2 cell-mediated immune diseases such as allergic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Berberine / pharmacology*
  • CD40 Ligand / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis*
  • Interleukin-12 / immunology
  • Interleukin-4 / biosynthesis
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred DBA
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*


  • Antibodies, Monoclonal
  • Berberine
  • CD40 Ligand
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma