The authors have no conflict of interest.
Effect of Crohn's Disease on Bone Metabolism In Vitro: A Role for Interleukin-6†
Version of Record online: 1 APR 2002
Copyright © 2002 ASBMR
Journal of Bone and Mineral Research
Volume 17, Issue 4, pages 695–702, April 2002
How to Cite
Sylvester, F. A., Wyzga, N., Hyams, J. S. and Gronowicz, G. A. (2002), Effect of Crohn's Disease on Bone Metabolism In Vitro: A Role for Interleukin-6. J Bone Miner Res, 17: 695–702. doi: 10.1359/jbmr.2002.17.4.695
- Issue online: 2 DEC 2009
- Version of Record online: 1 APR 2002
- Manuscript Accepted: 8 OCT 2001
- Manuscript Revised: 21 AUG 2001
- Manuscript Received: 25 FEB 2001
- Crohn's disease;
- inflammatory bowel disease;
Circulating proinflammatory cytokines may be involved in osteopenia associated with Crohn's disease (CD). Therefore, the effect of interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF) α contained in Crohn's serum on bone formation was examined in a bone organ culture system. Initially, serum levels of IL-6, IL-1β, and TNF-α 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-1β and TNF-α 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-α and IL-1β 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.