Activity of interleukin 6 in the differentiation of monocytes to macrophages and dendritic cells

Peripheral blood monocytes are common precursor cells of dendritic cells (D Cs) and macrophages. We have searched for factors with the potential to reg ulate the differentiation of monocytes to DCs and macrophages. When CD14(+) monocytes are cultured with granulocyte-macrophage colony-stimulating fact or (GM-CSF) and interleukin (IL) 4, the CD14(+)CD1a(-) population, which co nsists of macrophages, was found in the serum-containing cultures but not i n the serum-fret cultures. Addition of IL-6 receptor-neutralizing monoclona l antibody (mAb) or gp130-neutralizing mAb to the serum-containing cultures resulted in a decreased population of CD 14(+)CD1a(-) cells. An increase i n the CD14(+)CD1a(-) population with reduction in CD14(-)CD1a(+) DCs was ob served with the addition of IL-6 to cultures, whereas IL-11, leukaemia inhi bitory factor, oncostatin M or macrophage colony-stimulating factor did not affect the differentiation of monocytes in the presence of GM-CSF plus IL- 4. This effect elf of IL-6 was blocked by tumour necrosis factor alpha (TNF -alpha), lipopolysaccharide (LPS), IL-1 beta, CD40 ligand (CD40L) and trans forming growth factor pi (TGF-beta 1). Among these factors, TNF-alpha was m ost potent in interfering with the action of IL-6. These results suggest th at IL-6 inhibits the differentiation of monocytes to DCs by promoting their differentiation toward macrophages, which is modulated by factors such as TNF-alpha, LPS, IL-1 beta, CD40L and TGF-beta 1.