Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease

Gastroenterology. 1995 May;108(5):1434-44. doi: 10.1016/0016-5085(95)90692-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / therapy
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / genetics
  • Interleukin-1 / metabolism
  • Interleukin-10 / pharmacology
  • Interleukin-10 / physiology*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Monocytes / immunology
  • Monocytes / metabolism
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Sialoglycoproteins / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • RNA, Messenger
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10