Gastroenterology

Gastroenterology

Volume 108, Issue 5, May 1995, Pages 1434-1444
Gastroenterology

Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease

https://doi.org/10.1016/0016-5085(95)90692-4Get rights and content

Abstract

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] α and IL-1β) expression in IBD in vitro and in vivo. Methods IL-10 regulation of IL-1β, TNF-α, 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-1β and TNF-α 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-1β 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.

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    Supported by a grant from the Deutsche Forschungsgemeinschaft (DFG 512/3-4) (to S.S.).

    Parts of this work have been presented at the 95th annual meeting of the American Gastroenterological Association, New Orleans, Louisiana.

    1

    Dr. Schreiber's present address is: Fourth Medical Department, Charité (Humboldt University), Berlin, Germany.

    2

    Dr. Raedle's present address is: Department of Medicine, Tabea Hospital, Hamburg, Germany.

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