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Th1-MEDIATED INTESTINAL INFLAMMATION IN CROHN’S DISEASE M AY BE INDUCED BY ACTIVATION OF LAMINA PROPRIA LYMPHOCYTES THROUGH SYNERGISTIC STIMULATION OF INTERLEUKIN-12 AND IN TERLEUKIN-18 WITHOUT T CELL RECEPTOR ENGAGEMENT

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  • Sarah Krein
    Th1-MEDIATED INTESTINAL INFLAMMATION IN CROHN’S DISEASE MAY BE INDUCED BY ACTIVATION OF LAMINA PROPRIA LYMPHOCYTES THROUGH SYNERGISTIC STIMULATION OF
    Message 1 of 1 , Jan 4, 2003
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      Th1-MEDIATED INTESTINAL INFLAMMATION IN CROHN�S DISEASE MAY BE INDUCED BY
      ACTIVATION OF LAMINA PROPRIA LYMPHOCYTES THROUGH SYNERGISTIC STIMULATION OF
      INTERLEUKIN-12 AND INTERLEUKIN-18 WITHOUT T CELL RECEPTOR ENGAGEMENT

      OBJECTIVE:
      The development of T helper type 1 (Th1) CD4+ T cells in the intestinal
      mucosa is driven by interleukin (IL)-12 produced from activated macrophages
      and IL-18 produced from activated macrophages and epithelial cells. Each of
      these two cytokines is important for the mucosal response during intestinal
      inflammation, but their synergistic effect is not fully understood. To
      characterize the synergistic effect of IL-12 and IL-18 with respect to human
      intestinal inflammation, we assessed the effect of IL-12 and IL-18 on lamina
      propria lymphocytes from normal control subjects (LPL-NL) and patients with
      Crohn�s disease (LPL-CD).
      METHODS:
      Expression of IL-12 receptor (IL-12R) ?1, ?2, and IL-18R? in LPLs was
      analyzed by flow cytometry. The functional activity of IL-12 and IL-18 was
      assessed by the effect of recombinant IL-12 and recombinant IL-18 on
      interferon-? production, the proliferative response, and the induction of
      IL-2R, IL-12R, and IL-18R of LPLs.
      RESULTS:
      IL-12R?2 expression was significantly greater in LPL-CD compared with LPL-NL
      LPL-NL demonstrated a proliferative response and a significant increase in
      interferon-? production and IL-2R? expression when exposed to both IL-12 and
      IL-18, but neither IL-12 nor IL-18 were able to induce this response on
      their own. However, IL-12 and IL-18 produced this response in LPL-CD when
      administered alone. Moreover, a more pronounced synergistic effect of IL-12
      and IL-18 was observed in LPL-CD. The response normally observed after
      administration of IL-12 and IL-18 was significantly inhibited by anti-IL-2
      and anti-IL-2R? monoclonal antibody. Furthermore, IL-12 was observed to
      upregulate IL-18R? expression in LPL-CD.
      CONCLUSIONS:
      These findings suggest that a combination of IL-12 and IL-18 in the absence of T cell receptor engagement may serve as a potent regulatory factor for LPL and contribute to the maintenance and enhancement of chronic inflammation in CD.
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