Interleukin 1β (IL-1β) levels are elevated in the colonic mucosa of patients with ulcerative colitis (UC). We propose that IL-1β may also be elevated in the circular muscle layer of the colon and may be partially responsible for the motility dysfunction observed in patients with UC.
Cohort analytic study.
Research laboratory in a tertiary academic medical center.
Normal smooth muscle was obtained from the disease-free margins of human sigmoid colon specimens resected from patients with cancer and compared with specimens from patients with UC.
An enzyme-linked immunosorbent assay was used to measure IL-lβ. Standard muscle chambers were used to measure force changes. Single muscle cells were isolated by enzymatic digestion, and cell shortening in response to neurokinin A (NKA) and thapsigargin was measured under a microscope. Cytosolic Ca2+ (calcium) concentrations were measured by standard techniques.
Main Outcome Measure
Effects of IL-1β on smooth muscle function in normal and UC colons.
In patients with UC, IL-1β was elevated in the muscularis propria, and sigmoid circular smooth muscle contractions in response to NKA and thapsigargin were significantly reduced. In fura-2–loaded cells from patients with UC, the NKA-induced Ca2+ signal was also significantly reduced in Ca2+-free medium, indicating the reduced intracellular Ca2+ stores after UC. Exposure of normal cells to IL-1β mimicked the changes observed in patients with UC. An IL-1β–induced reduction in contraction and release of intracellular Ca2+ in response to NKA was partially restored by the hydrogen peroxide scavenger catalase.
In patients with UC, IL-1β was increased in colonic circular muscles and may contribute to motor dysfunction after UC through production of hydrogen peroxide.