Effect of Crohn's disease on bone metabolism in vitro: a role for interleukin-6

J Bone Miner Res. 2002 Apr;17(4):695-702. doi: 10.1359/jbmr.2002.17.4.695.


Circulating proinflammatory cytokines may be involved in osteopenia associated with Crohn's disease (CD). Therefore, the effect of interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF) a contained in Crohn's serum on bone formation was examined in a bone organ culture system. Initially, serum levels of IL-6, IL-1beta, and TNF-a were determined by ELISA in newly diagnosed, untreated children with CD and healthy age-matched controls. Serum IL-6 levels were significantly higher in patients with CD than in controls (23.9 +/- 2.8 pg/ml vs. 0.7 pg/ml +/- 0.2; p < 0.001), whereas IL-1beta and TNF-alpha serum levels were not. In the organ culture studies, 20-day-old fetal rat parietal bones were incubated for 96 h with CD or control serum, serum preincubated with a neutralizing antibody to each cytokine or a nonimmune immunoglobulin control, and with IL-6. Bone formation measured by assaying calcium content and dry weight was significantly decreased in bones exposed to Crohn's serum. Light microscopy of the bones treated with CD serum revealed a discontinuous, uneven mineralized bone matrix and disorganized osteoblasts with altered morphology. Incubation with an antibody that neutralized IL-6 activity prevented the change in osteoblast and bone morphology. TNF-a and IL-1beta antibodies had no apparent effects. Collagen synthesis and DNA content were not affected by CD serum. Also, addition of IL-6 to the culture medium decreased mineralization. These results suggest that IL-6 is a mediator of the effects of Crohn's serum on in vitro mineralization and may be a contributing factor to the osteopenia associated with CD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Bone Diseases, Metabolic / etiology
  • Bone Diseases, Metabolic / metabolism
  • Bone and Bones / metabolism*
  • Case-Control Studies
  • Child
  • Crohn Disease / complications
  • Crohn Disease / metabolism*
  • Crohn Disease / physiopathology
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Interleukin-1 / blood
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Male
  • Organ Culture Techniques / methods
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Parietal Bone / embryology
  • Parietal Bone / metabolism
  • Rats
  • Receptors, Interleukin-6 / blood
  • Tumor Necrosis Factor-alpha / metabolism


  • Antibodies, Monoclonal
  • Interleukin-1
  • Interleukin-6
  • Receptors, Interleukin-6
  • Tumor Necrosis Factor-alpha