Nicotinamide decreases cytokine-induced activation of orbital fibroblasts from patients with thyroid-associated ophthalmopathy

J Clin Endocrinol Metab. 1998 Jan;83(1):121-4. doi: 10.1210/jcem.83.1.4478.


We used flow cytometry to investigate the effects of nicotinamide, an inhibitor of poly (ADP ribose) synthetase, on the cell-surface expression of cytokine-induced human leukocyte antigen (HLA)-A,B,C antigen, HLA-DR antigen, intercellular adhesion molecule 1, CD44, and Fas expression in cultured orbital fibroblasts from patients with thyroid-associated ophthalmopathy. After two to seven passages, cultured orbital fibroblasts were incubated for 3 days with interferon gamma or tumor necrosis factor alpha in the presence of nicotinamide. Nicotinamide inhibited the induction of both HLA-DR and intercellular adhesion molecule 1 expression by cytokines on fibroblasts but did not interfere with induction of HLA-A,B,C, or CD44 expression. Nicotinamide also inhibited the proliferation of orbital fibroblasts, as assessed by a [3H]-thymidine incorporation assay and cell counts. Nicotinamide also enhanced the expression of the apoptosis-mediating protein Fas on fibroblasts. Our data suggest that nicotinamide inhibits cytokine-induced activation of fibroblasts and thus may decrease the autoimmune injury to the orbit in thyroid-associated ophthalmopathy.

MeSH terms

  • Adipose Tissue / enzymology*
  • Adipose Tissue / pathology
  • Cell Division / drug effects
  • Cells, Cultured
  • Cytokines / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Graves Disease / immunology*
  • HLA-A Antigens / biosynthesis
  • HLA-B Antigens / biosynthesis
  • HLA-C Antigens / biosynthesis
  • HLA-DR Antigens / biosynthesis*
  • Histocompatibility Antigens Class I / biosynthesis*
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interferon-gamma / pharmacology
  • Niacinamide / pharmacology*
  • Orbit
  • Skin / drug effects
  • Skin / immunology
  • Tumor Necrosis Factor-alpha / pharmacology
  • fas Receptor / biosynthesis


  • Cytokines
  • HLA-A Antigens
  • HLA-B Antigens
  • HLA-C Antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class I
  • Hyaluronan Receptors
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Intercellular Adhesion Molecule-1
  • Niacinamide
  • Interferon-gamma