Transfer of Interleukin-4 and Interleukin-10 in Patients with Severe Inflammatory Bowel Disease of the Rectum Academic Article uri icon

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abstract

  • Inflammatory bowel disease (IBD) comprises the two disorders ulcerative colitis (UC) and Crohn's disease (CD). Although the etiology is still unclear, initiation and aggravation of the inflammatory processes seem to be due to a massive local mucosal immune response. An increased number of greatly activated macrophages seems to contribute to the onset of IBD by expressing upregulated costimulatory molecules (e.g., CD80/CD86) and a cytokine profile favouring a type I proinflammatory response. The release of interleukin 2 (IL-2) and Interferon-gamma (IFN-gamma) by naive T lymphocytes predominantly stimulates cytotoxic T lymphocytes, macrophages, and natural killer (NK) cells and increases the antigen-presenting potential of all these cell types. Opposite this proinflammatory immune reaction a compensatory type II antiinflammatory response has been suggested in the inflamed mucosa, involving mainly interleukin 4 and interleukin 10. Both cytokines are able to down-regulate inflammatory mediators including tumor necrosis factor-alpha (TNF-alpha) and interleukin 1 and favor a humoral immune response. The main goal of this clinical trial is the local liposome-mediated gene transfer of these two antiinflammatory cytokines, interleukin 4 and interleukin 10, in patients with severe IBD of the rectum. This local administration of antiinflammatory cytokines will avoid toxic systemic side effects, prevents blocking of the beneficial effects of proinflammatory cytokines, e.g., TNF-alpha in other tissue compartments and increases the local concentration of interleukin 4 and interleukin 10 over a prolonged period of time. The combined effects of IL-4 and IL-10 have been shown to shift the Th1/Th2 cell activation in favor of a Th2 immune response which seems to be essential for fighting against the inflammation and ultimative healing.

authors

  • Rogy, Michael A
  • Beinhauer, Brigitte G
  • Reinisch, Walter
  • Huang, Leaf
  • Pokieser, Peter

publication date

  • August 10, 2000