The mechanism of altered neural function in a rat model of acute colitis.
OBJECTIVE
Distal colitis induced in rats by trinitrobenzene sulfonic acid (TNBS) causes a suppression of [3H]noradrenaline release from the myenteric plexus, of inflamed distal colon, as well as in noninflamed regions of colon and ileum. The aim of this study was to explore the mechanisms underlying these neural changes in TNBS colitis.


METHODS
Colitis was induced by intrarectal administration of TNBS, and the animals were killed on day 5. Inflammation was assessed by measuring myeloperoxidase (MPO) activity, and noradrenaline release was measured as 3H release from rats myenteric plexus preparations preloaded with [3H]noradrenaline. These end points were examined: (1) after administration of the locally active steroid budesonide; (2) in congenitally athymic rats; and (3) in rats treated with the interleukin 1 receptor antagonist (IL-1ra) to interleukin 1 beta.


RESULTS
In colitis, both topical budesonide and systemic IL-1ra treatments attenuated the suppression of KCl-evoked 3H release from longitudinal muscle myenteric plexus in both inflamed and noninflamed segments. However, neither of these treatments altered MPO activity. A similar suppression of [3H]noradrenaline release was observed in athymic rats after TNBS, although there was a substantially greater increase in MPO activity compared with euthymic rats with colitis.


CONCLUSIONS
TNBS-induced colitis alters myenteric nerve function at inflamed and noninflamed sites via a steroid-sensitive and interleukin 1-mediated process that does not require T lymphocytes.
Jacobson
K
K
Department of Medicine, McMaster University Medical Centre, Hamilton, Ontario, Canada.
McHugh
K
K
Collins
S M
SM
D000208:Acute Disease; D000287:Administration, Topical; D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019819:Budesonide; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D003106:Colon / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism; D005938:Glucocorticoids; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011282:Pregnenediones / Q000494:pharmacology*; D011292:Premedication; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D011282:Pregnenediones; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D019819:Budesonide; D011189:Potassium Chloride; D014302:Trinitrobenzenesulfonic Acid; D009638:Norepinephrine