Inflammatory Mediators in Inflammatory Bowel Disease

Tissue responses to an inflammatory stimulus (such as vasodilation, plasma exudation invasion and activation of inflammatory cells) are elicited by locally synthesized chemical mediators. Inhibition of biosynthesis and/or antagonism of action of these mediators is an important target of drug therapy...

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Bibliographic Details
Main Author: BM Peskar
Format: Article
Language:English
Published: Wiley 1990-01-01
Series:Canadian Journal of Gastroenterology
Online Access:http://dx.doi.org/10.1155/1990/362497
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Summary:Tissue responses to an inflammatory stimulus (such as vasodilation, plasma exudation invasion and activation of inflammatory cells) are elicited by locally synthesized chemical mediators. Inhibition of biosynthesis and/or antagonism of action of these mediators is an important target of drug therapy, particularly when the cause of the disease is unknown. Recent investigations have revealed that the mucosa of inflammatory bowel disease (IBD) patients synthesizes a number of inflammatory mediators in increased amounts. These include the potent chemoattractant leukotricne B4, which seems to be responsible for the increase in chemotactic activity found in IBO mucosa, and the cysteinyl leukotrienes, which promote plasma leakage and induce edema formation. Synthesis of leukotrienes in normal and inflamed mucosa is dose-dependently inhibited by sulphasalazine, 5-aminosalicylic acid (5-ASA) and 4-aminosalicylic acid, while indomethacin, which is devoid of therapeutic efficacy in IBD patients, inhibits prostaglandin hut not leukotriene synthesis. These findings suggest that in IBD, mucosal leukotrienes may be more important inflammatory mediators than prostaglandins. ln addition to arachidonic acid-derived products, IBD mucosa generates platelet activating factor and various cytokines including interleukin-1 and tumour necrosis factor, all of which have potent proinflammatory actions. formation of most of these agents is inhibited by sulphasalazine and 5-ASA. The relative importance and the interactions of the various inflammatory mediators synthesized in IBD mucosa remain to be clarified.
ISSN:0835-7900