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


METHODS
Cohort analytic study.


METHODS
Research laboratory in a tertiary academic medical center.


METHODS
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Vrees
Matthew D
MD
Department of Surgery, Rhode Island Hospital and Brown University School of Medicine, 593 Eddy St, Providence, RI 02903, USA.
Pricolo
Victor E
VE
Potenti
Fabio M
FM
Cao
Weibiao
W
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors; D002118:Calcium / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000503:physiopathology*; D003106:Colon / Q000503:physiopathology*; D012809:Colon, Sigmoid / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000503:physiopathology; D003600:Cytosol / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005769:Gastrointestinal Motility; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015288:Neurokinin A / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D007375:Interleukin-1; D019284:Thapsigargin; D015288:Neurokinin A; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D002118:Calcium