Osteopontin, a protein with cytokine-like properties, is associated with inflammation in Crohn's disease

Scand J Immunol. 2007 May;65(5):453-60. doi: 10.1111/j.1365-3083.2007.01908.x.


In Crohn's disease (CD) mucosal T-cells produce increased interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) levels and TNF-alpha antibody treatment [Infliximab (Ifx)] is effective. Osteopontin (OPN), a glycoprotein stimulating activated T-lymphocytes, may be involved in the disturbed immune-regulation but also in normal immune-homeostasis and mucosal repair, since it is expressed in many tissues and present in human milk. This study investigates plasma-OPN levels in CD patients during Ifx treatment and the in vitro effect of OPN on intestinal T cells. Thirty-seven CD patients received three Ifx doses at week 0, 2 and 6. Blood samples, colonic biopsies and clinical scores were obtained before treatment and at week 8, 26 and 52. In-vivo activated T-cell cultures were established from colonic biopsies in the presence of interleukin (IL)-2 and IL-4. The in vitro effect of OPN stimulation on T-cell IFN-gamma, TNF-alpha, and IL-10 production was measured. Plasma-OPN was increased in active CD (increased CRP-level) compared with quiescent disease (P = 0.02) and declined after three Ifx doses (P = 0.04). It was inversely correlated with in vitro T-cell IL-10 production. OPN increased CD69 and CD25 expression and enhanced T-cell IFN-gamma and TNF-alpha production in a dose-dependent fashion with higher levels in CD than in healthy controls (HC), but induced a concomitant higher IL-10 production in HC than CD. In conclusion, plasma-OPN levels are related to CD inflammation. In vitro, OPN-stimulated IL-10 production increases less in T-cell cultures from CD patients than from HC, indicating that IL-10 deficiency may be involved in the defect immune-regulation in CD, even after OPN stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Cells, Cultured
  • Crohn Disease / immunology
  • Crohn Disease / metabolism*
  • Crohn Disease / pathology*
  • Crohn Disease / therapy
  • Cytokines / blood
  • Cytokines / physiology*
  • Female
  • Humans
  • Inflammation Mediators / physiology*
  • Infliximab
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / deficiency
  • Interleukin-10 / metabolism
  • Male
  • Middle Aged
  • Osteopontin / blood
  • Osteopontin / physiology*
  • T-Lymphocytes / metabolism


  • Antibodies, Monoclonal
  • Cytokines
  • Inflammation Mediators
  • Osteopontin
  • Interleukin-10
  • Infliximab