IMMUNOREGULATORY PROPERTIES OF IL-13 IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE - COMPARISON WITH IL-4 AND IL-10

Activated monocytes with increased expression of proinflammatory cytok ines play a major role in inflammatory bowel disease (IBD). Immunoregu latory cytokines such as IL-4 and IL-10 can effectively suppress the p roinflammatory response of activated monocytes. IL-13 is a recently de scribed antiinflammatory agent in vitro. The aim of our study was to d etermine the in vitro immunosuppressive capacity of IL-13, IL-4 and IL -10 in patients with IBD. Peripheral blood monocytes were isolated fro m 27 patients with ulcerative colitis (UC), 27 patients with Crohn's d isease (CD) and 16 healthy controls. Cells were stimulated with pokewe ed mitogen (PWM) after treatment with IL-13, IL-4 and IL-10, and secre tion of IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and IL-6 w as assessed using sandwich ELISA systems. Peripheral blood monocytes s ecreted significantly increased amounts of TNF-alpha and IL-6 under st imulation with PWM in patients with CD, while UC patients showed signi ficantly elevated levels of IL-1 beta. The antiinflammatory cytokines IL-13, IL-4 and IL-10 were all capable of inhibiting monocyte secretio n of IL-1 beta in a dose-dependent manner. With regard to IL-13 and IL -4, there was no significant suppression of TNF-alpha and IL-6 in pati ents with active IBD. By contrast, IL-10 was able to downregulate all proinflammatory cytokines in active IBD as well as in controls. Proinf lammatory cytokines from patients with inactive IBD could be significa ntly down-regulated by all three immunoregulatory cytokines. The inhib itory effect of IL-13 on TNF-alpha and IL-6 production in differentiat ed macrophages was diminished in IBD patients, as well as in controls. In disease controls we also observed a reduced inhibition of TNF-alph a and IL-6 after treatment with IL-13. In conclusion, the antiinflamma tory activity of IL-13 is partially reduced in patients with active IB D. The hyporesponsiveness of activated and differentiated monocytes to IL-13 and IL-4 does not seem to be a disease-specific phenomenon.