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 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.
Rogy
M A
MA
Department of General Surgery, University of Surgery, AKH-Vienna, Austria.
Beinhauer
B G
BG
Reinisch
W
W
Huang
L
L
Pokieser
P
P
D002986:Clinical Trials as Topic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000628:therapy*; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics* / Q000378:metabolism; D008081:Liposomes; D018579:Patient Selection; D012002:Rectal Diseases / Q000276:immunology / Q000628:therapy*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4