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Arch Surg. 2002 Apr;137(4):439-45; discussion 445-6.

Abnormal motility in patients with ulcerative colitis: the role of inflammatory cytokines.

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  • 1Department of Surgery, Rhode Island Hospital and Brown University School of Medicine, 593 Eddy St, Providence, RI 02903, USA.

Abstract

HYPOTHESIS:

Interleukin 1 beta (IL-1 beta) levels are elevated in the colonic mucosa of patients with ulcerative colitis (UC). We propose that IL-1 beta 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.

DESIGN:

Cohort analytic study.

SETTING:

Research laboratory in a tertiary academic medical center.

PARTICIPANTS:

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.

INTERVENTIONS:

An enzyme-linked immunosorbent assay was used to measure IL-l beta. 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 Ca(2+) (calcium) concentrations were measured by standard techniques.

MAIN OUTCOME MEASURE:

Effects of IL-1 beta on smooth muscle function in normal and UC colons.

RESULTS:

In patients with UC, IL-1 beta 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 Ca(2+) signal was also significantly reduced in Ca(2+)-free medium, indicating the reduced intracellular Ca(2+) stores after UC. Exposure of normal cells to IL-1 beta mimicked the changes observed in patients with UC. An IL-1 beta-induced reduction in contraction and release of intracellular Ca(2+) in response to NKA was partially restored by the hydrogen peroxide scavenger catalase.

CONCLUSION:

In patients with UC, IL-1 beta was increased in colonic circular muscles and may contribute to motor dysfunction after UC through production of hydrogen peroxide.

PMID:
11926949
[PubMed - indexed for MEDLINE]
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