High levels of proinflammatory cytokines, but not markers of tissue injury, in unaffected intestinal areas from patients with IBD

Mediators Inflamm. 2009;2009:580450. doi: 10.1155/2009/580450. Epub 2009 Jul 30.


Intestinal alterations in IBD are triggered and maintained by an overexpression of proinflammatory cytokines. Additionally, increased immune activation has been found in the adjacent intestinal areas without displaying any apparent histological alterations, however, the regulatory environment is not well established. Biopsy specimens from patients with ulcerative colitis (UC) and Crohn's disease (CD), from both affected and unaffected areas, and also from a group of colonic biopsies from healthy controls, were included in our study. Cytokines and markers of mucosal damage were analyzed by real-time PCR, and some of the results confirmed by western-blot and ELISA. Levels of IFNgamma, TNFalpha, IL-6, IL-15, IL-18, and IL-23 were increased (above healthy controls) in both affected and unaffected areas from IBD. IL-1beta, IL-6, IL-12, and IL-27 were higher in affected areas compared to unaffected ones in UC but not CD. In general, a correlation was observed between mRNA levels of these cytokines and both iNOS and Granzyme B. SOCS-2 and SOCS-3 were also increased in the affected areas. In conclusion, the unaffected areas from IBD show increased levels of a restricted set of cytokines that may exert immune activating roles in these areas without being able to trigger tissue damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blotting, Western
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism
  • Crohn Disease / genetics
  • Crohn Disease / immunology
  • Crohn Disease / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / metabolism*
  • Interferon-gamma / genetics
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism
  • Interleukin-18 / genetics
  • Interleukin-18 / metabolism
  • Interleukin-23 / genetics
  • Male
  • Matrix Metalloproteinase 3 / genetics
  • Nitric Oxide Synthase Type II / genetics
  • Polymerase Chain Reaction
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Young Adult


  • Interleukin-15
  • Interleukin-18
  • Interleukin-23
  • SOCS2 protein, human
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Tissue Inhibitor of Metalloproteinase-1
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Nitric Oxide Synthase Type II
  • Matrix Metalloproteinase 3