Oxygen free radicals in interleukin-1beta-induced glycosaminoglycan production by retro-ocular fibroblasts from normal subjects and Graves' ophthalmopathy patients

Thyroid. 1999 Mar;9(3):297-303. doi: 10.1089/thy.1999.9.297.


Graves' ophthalmopathy (GO) is attributed to an autoimmune process that results in the accumulation in retro-ocular tissue of glycosaminoglycans (GAG) that are in turn responsible for the development of clinical signs and symptoms. Retro-ocular fibroblasts are thought to be the source of GAG production and deposition in GO. In the present study, we investigated interleukin (IL)-1beta-induced oxygen free radical production and the role of oxygen free radicals in IL-1beta-induced GAG production in retro-ocular fibroblasts from both normal subjects and patients with GO. Normal retro-ocular fibroblasts demonstrated no measurable oxygen free radicals whereas GO retro-ocular fibroblasts showed detectable signals by electron paramagnetic resonance (EPR) spectroscopy. IL-1beta increased the free radical production in both cells. Superoxide dismutase (SOD) activity in GO retroocular fibroblasts was higher than that in normal cells. IL-1beta dose- and time-dependently stimulated the SOD activity in both cells, with GO retro-ocular fibroblasts showing less responsiveness. IL-1beta dose-dependently increased [3H]glucosamine incorporation into GAG by both cells. An exogenous oxygen free radical-generating system failed to increase GAG. Scavenging oxygen free radicals by the use of SOD (100 U/mL) and catalase (300 U/mL) partially blocked the IL-1beta-induced GAG production in both cells. These results suggest that stress related oxygen free radicals are present in the retro-ocular tissue in GO and that oxygen free radicals are involved in GAG accumulation induced by cytokine IL-1beta.

MeSH terms

  • Catalase / pharmacology
  • Cells, Cultured
  • Cyclic N-Oxides / metabolism
  • Dose-Response Relationship, Drug
  • Electron Spin Resonance Spectroscopy
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Glycosaminoglycans / biosynthesis*
  • Graves Disease / metabolism*
  • Humans
  • Hypoxanthine / pharmacology
  • Interleukin-1 / pharmacology*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase / pharmacology
  • Superoxides / metabolism*
  • Time Factors
  • Xanthine Oxidase / pharmacology


  • Cyclic N-Oxides
  • Glycosaminoglycans
  • Interleukin-1
  • Superoxides
  • Hypoxanthine
  • 5,5-dimethyl-5-hydroperoxy-1-pyrrolidinyloxy
  • Catalase
  • Superoxide Dismutase
  • Xanthine Oxidase