Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody

Ivan J. Fuss, Christoph Becker, Zhiqiong Yang, Catherine Groden, Ronald L. Hornung, Frank Heller, Markus F. Neurath, Warren Strober, Peter J. Mannon

Research output: Contribution to journalArticlepeer-review

150 Scopus citations


Background: Interleukin (IL)-12p70 and IL-23 are key T helper-1 (T H1) cytokines that drive the inflammation seen in numerous models of intestinal inflammation. These molecules contain an identical p40 chain that is bound to a p35 chain in IL-12 and a p19 chain in IL-23, making both potentially susceptible to modulation by an anti-IL-12p40 monoclonal antibody (mAb). Methods: In the present study, we sought to determine whether active inflammation hi Crohn's disease (CD) is associated with the increased synthesis of both of these cytokines and whether patients treated with an anti-IL-12p40 mAb down-regulate IL-23 as well as IL-12p70 as previous reported. Results: To this end we initially determined that IL-12p70 secretion by control and CD antigen-presenting cells (macrophages) in lamina propria mononuclear populations is optimized by stimulation with CD40L and interferon-γ. In subsequent studies using these stimulation conditions we found that patients with CD manifested both increased IL-12p70 and IL-23 secretion before anti-IL-12p40 mAb treatment and normal levels of secretion of these cytokines following cessation of treatment. Antigen-presenting cells in lamina propria mononuclear cells from ulcerative colitis patients, in contrast, produced only baseline levels of IL-23. Finally, we found that IL-23-induced T cell production of IL-17 and IL-6 are also greatly reduced after antibody treatment. The latter data are parallel to those from previous studies showing that anti-IL-12p40 down-regulates IFN-γ and tumor necrosis factor-α secretion. Conclusions: We conclude that CD but not ulcerative colitis is associated with high levels of both IL-12p70 and IL-23 secretion as well as the secretion of downstream effector cytokines, and that this cytokine production is down-regulated following administration of IL-12p40 mAb.

Original languageEnglish (US)
Pages (from-to)9-15
Number of pages7
JournalInflammatory Bowel Diseases
Issue number1
StatePublished - Jan 2006
Externally publishedYes


  • Inflammatory bowel diseases
  • Interleukin-12
  • Interleukin-23

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology


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