# Modulation Of Gatsrointestinal Motility By Interleukins



## Mike NoLomotil (Jun 6, 2000)

INRA is the Institut National de la Recherche Agronomique, a national scientific and technological research establishment under the auspices of the Ministry of Higher Education and Research of the French government. They have research dept.s of various soecialties throughout universities. medical schools, and other instituions throughout France. The Pharmacology Dept. has done extensive work in this area and the following tutorial from that Department explains the origin of this CRF phenomenon based upon the whole of current summative research. This tutorial explains the underlying influence of interleukin 1b on central CRF levels and peripherpheral effects in controlling gut motility.---------------------------------------------MODULATION OF GASTROINTESTINAL MOTILITY BY INTERLEUKINS.L. Buï¿½noDepartment of Pharmacology, INRA, Toulouse, France.There is now mounting evidence that IL1b locally released during gut inflammatory processes may influence sensitivity and motility by acting directly on nerve terminals and intrinsic neurons, but also through an activation of local immunocytes. However, cytokines released at CNS level in response to peripheral inflammatory stimulus may also act on brain structures to influence gastrointestinal and colonic motility.The action of centrally administered IL1b is linked to the CNS release of prostaglandins and corticotropin-releasing factor (CRF), their release being mediated through activation of both adrenergic and nitrergic pathways. While brain prostaglandins are responsible of the IL1b-induced inhibition of the upper gut motility, IL1b evokes a colonic motor stimulation linked to the brain release of CRF and the subsequent activation of vasopressin containing neurons which activate efferent nerves and the peripheral release of 5HT.In septic shock, the upper gut motor inhibition following intraperitoneal administration of E. Coli endotoxin is, in part, linked to a vagally driven CNS release of IL1b. Similarly colonic transit and motor activation observed in antigenic challenge in ovalbumin sensitized rats or b-lactoglobulin-sensitized guinea pig are suppressed by centrally administered IL1-ra, a IL1 receptor antagonist, these effects being mimicked by central administration of IL1b.Alterations in colonic motility occurring 2 to 7 days after intraluminal infusion of TNBS are transiently suppressed by peripheral IL1-ra administration suggesting a permanent role of IL1b in maintaining abnormal colonic motor pattern in rats under inflammatory conditions.Prolonged rectal distension is associated with an overexpression of IL1b at brain level and the colonic secretory reflex initiated by rectal distension is abolished after intracerebroventricular but not systemic administration of IL1-ra. This result suggests that IL1b may be released in response to a non-infectious stimulus. Similarly stress-induced activation of the synthesis of mediators such as histamine by mucosal mast cell also depends upon the central release of IL1.We conclude that interleukins and particularly IL1 play a major role in the modulation of gut motility in physiopathological situations by acting at different level (afferent, and afferent nerves or brain) to modulate functional visceral


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## Mike NoLomotil (Jun 6, 2000)

Bumpt to INRA Tutorial on Inflammatory Mediators and the gut[This message has been edited by Mike NoLomotil (edited 09-11-2000).]


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