Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease.

BACKGROUND/AIMS: Active inflammatory bowel disease (IBD) is associated with increased proinflammatory cytokines. Deficiency of interleukin (IL) 10, a contrainflammatory cytokine, leads to the development of colitis in IL-10 knockout mice. We characterized IL-10 regulation of proinflammatory cytokine (tumor necrosis factor [TNF] alpha and IL-1 beta) expression in IBD in vitro and in vivo.

METHODS

IL-10 regulation of IL-1 beta, TNF-alpha, and IL-1 receptor antagonist expression by peripheral monocytes or isolated lamina propria mononuclear cells (LPMNC), respectively, was studied by enzyme-linked immunosorbent assay (cytokine secretion) and by semiquantitative reverse-transcription polymerase chain reaction.

RESULTS

IL-10 down-regulates IL-1 beta and TNF-alpha secretion as well as messenger RNA levels in IBD peripheral monocytes and LPMNC in a dose-dependent manner. In parallel, IL-1 receptor antagonist secretion is induced, and IL-10 can restore diminished in vitro IL-1 receptor antagonist/IL-1 beta ratios in IBD to normal levels. Equal concentrations of IL-10 are detectable in both normal and IBD intestinal lamina propria biopsy homogenates. After topical IL-10 enema treatment of three steroid therapy-refractory patients with ulcerative colitis, in vitro release of proinflammatory cytokines from IBD peripheral monocytes as well as LPMNC is dramatically down-regulated.

CONCLUSIONS

IL-10 down-regulates the enhanced secretion as well as messenger RNA levels of proinflammatory cytokines by IBD mononuclear phagocytes in vitro. In vivo topical application of IL-10 induces down-regulation of proinflammatory cytokine secretion both systemically and locally.