Localization of intestinal interleukin 1 activity and protein and gene expression to lamina propria cells

Gastroenterology. 1993 Mar;104(3):749-58. doi: 10.1016/0016-5085(93)91010-f.

Abstract

Background: Interleukin 1 (IL-1) is a key mediator of bowel inflammation, but there is limited knowledge about the amount and site of production of this cytokine in the gastrointestinal tract under physiological or pathological conditions.

Methods: Epithelial and lamina propria mononuclear cells were isolated from control, and Crohn's disease- and ulcerative colitis-involved mucosa to investigate the capacity of these cells to generate IL-1 bioactivity, IL-1 alpha and IL-1 beta immunoreactivity, and gene expression.

Results: Control lamina propria mononuclear cells produced substantial amounts of IL-1 alpha and IL-1 beta, which increased dramatically when inflammatory bowel disease cells were used. Epithelial cells from control, Crohn's disease, and ulcerative colitis intestine displayed no IL-1 bioactivity or immunoreactivity. Lamina propria mononuclear cells contained moderate to large quantities of IL-1 alpha and IL-1 beta messenger RNA (mRNA), respectively, whereas epithelial cells had none. The absence of IL-1 transcripts in epithelial cells was selective, because mRNA for HLA-DR antigens was present in control and inflammatory bowel disease cells.

Conclusions: In normal and inflamed human intestine there is a distinct compartmentalization of IL-1, as mononuclear but not epithelial cells generate this cytokine. The high levels of IL-1 in inflammatory bowel disease may explain several of its local and systemic manifestations, and blockade by specific antagonists could have important therapeutic effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Colitis, Ulcerative / metabolism
  • Crohn Disease / metabolism
  • Female
  • Gene Expression
  • HLA-DR Antigens / genetics
  • Humans
  • Interleukin-1 / analysis*
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / genetics
  • Intestinal Mucosa / chemistry*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • RNA, Messenger / analysis

Substances

  • HLA-DR Antigens
  • Interleukin-1
  • RNA, Messenger