Immunoregulatory properties of IL-13 in patients with inflammatory bowel disease; comparison with IL-4 and IL-10

Abstract

SUMMARY Activated monocytes with increased expression of proinflammatory cytokines play a major role in inflammatory bowel disease (IBD). Immunoregulatory cytokines such as IL-4 and IL-10 can effectively suppress the proinflammatory response of activated monocytes. IL-13 is a recently described antiinflammatory agent in vitro. The aim of our study was to determine the in vitro immunosuppressive capacity of IL-13, IL-4 and IL-10 in patients with IBD. Peripheral blood monocytes were isolated from 27 patients with ulcerative colitis (UC), 27 patients with Crohn’s disease (CD) and 16 healthy controls. Cells were stimulated with pokeweed mitogen (PWM) after treatment with IL-13, IL-4 and IL-10, and secretion of IL-1β, tumour necrosis factor-alpha (TNF-α) and IL-6 was assessed using sandwich ELISA systems. Peripheral blood monocytes secreted significantly increased amounts of TNF-α and IL-6 under stimulation with PWM in patients with CD, while UC patients showed significantly elevated levels of IL-1β. The antiinflammatory cytokines IL-13, IL-4 and IL-10 were all capable of inhibiting monocyte secretion of IL-1β in a dose-dependent manner. With regard to IL-13 and IL-4, there was no significant suppression of TNF-α and IL-6 in patients with active IBD. By contrast, IL-10 was able to down-regulate all proinflammatory cytokines in active IBD as well as in controls. Proinflammatory cytokines from patients with inactive IBD could be significantly down-regulated by all three immunoregulatory cytokines. The inhibitory effect of IL-13 on TNF-α and IL-6 production in differentiated macrophages was diminished in IBD patients, as well as in controls. In disease controls we also observed a reduced inhibition of TNF-α and IL-6 after treatment with IL-13. In conclusion, the antiinflammatory activity of IL-13 is partially reduced in patients with active IBD. The hyporesponsiveness of activated and differentiated monocytes to IL-13 and IL-4 does not seem to be a disease-specific phenomenon.