Nicotinamide: a vitamin able to shift macrophage differentiation toward macrophages with restricted inflammatory features

Innate Immun. 2015 Nov;21(8):813-26. doi: 10.1177/1753425915602545. Epub 2015 Sep 18.


The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B3 derivative known to play a major role in nicotinamide adenine dinucleotide (NAD)-mediated signaling events, is able to modulate monocyte differentiation into macrophages developed in the presence of granulocyte macrophage colony-stimulating factor (GM-MØ) or macrophage colony-stimulating factor (M-MØ). We found that GM-MØ undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MØ were hardly affected. GM-MØ exposed to NAM acquired an M-MØ-like structure while the LPS-induced production of pro-inflammatory cytokines and COX-derived eicosanoids were down-regulated. In contrast, NAM had no effect on the production of IL-10 or the cytochrome P450-derived eicosanoids. Administration of NAM enhanced intracellular NAD concentrations; however, it did not prevent the LPS-mediated drain on NAD pools. In search of intracellular molecular targets of NAM known to be involved in LPS-induced cytokine and eicosanoid synthesis, we found NF-κB activity to be diminished. In conclusion, our data show that vitamin B3, when present during the differentiation of monocytes into GM-MØ, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features.

Keywords: Inflammation; LPS; NF-κB; macrophages; nicotinamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Eicosanoids / biosynthesis
  • Gene Expression Regulation / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor* / metabolism
  • Humans
  • Inflammation
  • Macrophage Colony-Stimulating Factor* / metabolism
  • Macrophages* / cytology
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Monocytes* / cytology
  • Monocytes* / immunology
  • Monocytes* / metabolism
  • NAD
  • NF-kappa B / metabolism
  • Niacinamide* / metabolism
  • Niacinamide* / pharmacology
  • Signal Transduction / drug effects
  • Vitamin B Complex* / metabolism
  • Vitamin B Complex* / pharmacology


  • Eicosanoids
  • NF-kappa B
  • NAD
  • Vitamin B Complex
  • Niacinamide
  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor