Transfer of interleukin-4 and interleukin-10 in patients with severe inflammatory bowel disease of the rectum

Inflammatory bowel disease (IBD) comprises the two disorders ulcerative col itis (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 ac tivated macrophages seems to contribute to the onset of IBD by expressing u pregulated 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 predominantl y stimulates cytotoxic T lymphocytes, macrophages, and natural killer (NK) cells and increases the antigen-presenting potential of all these cell type s. Opposite this proinflammatory immune reaction a compensatory type II ant iinflammatory response has been suggested in the inflamed mucosa, involving mainly interleukin 4 and interleukin 10, Both cytokines are able to downre gulate inflammatory mediators including tumor necrosis factor-alpha (TNF-al pha) and interleukin 1 and favor a humoral immune response, The main goal o f this clinical trial is the local liposome-mediated gene transfer of these two antiinflammatory cytokines, interleukin 4 and interleukin 10, in patie nts with severe LED of the rectum, This local administration of antiinflamm atory cytokines mill avoid toxic systemic side effects, prevents blocking o f the beneficial effects of proinflammatory cytokines, e.g., TNF-alpha in o ther tissue compartments and increases the local concentration of interleuk in 4 and interleukin 10 over a prolonged period of time. The combined effec ts of IL-4 and IL-10 have been shown to shift the Th1/Th2 cell activation i n favor of a Th2 immune response which seems to be essential for fighting a gainst the inflammation and ultimative healing.