LOCALIZATION OF INTESTINAL INTERLEUKIN-1 ACTIVITY AND PROTEIN AND GENE-EXPRESSION TO LAMINA PROPRIA CELLS

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-1α and IL-1β immunoreactivity, and gene expression. Results: Control lamina propria mononuclear cells produced substantial amounts of IL-1α and IL-1β, 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-1α and IL-1β 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. © 1993.