Abstract
Proinflammatory cytokines released from monocytes / macrophages, in particular tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and IL-8 seem to play an important role in Inflammatory Bowel Disease (ulcerative colitis and Crohns disease). Endotoxins or lipopolysaccharides, derived from the outer membrane of Gram-negative bacteria interact with CD14 on surface membrane of macrophages, thus triggering a signal cascade, which leads to the production and release of proinflammatory cytokines, particularly TNF-α. Therefore, in IBD, lipopolysaccharides could play a pathogenic role. In this respect, plasma endotoxins have been demonstrated in a not negligible percentage of patients with ulcerative colitis and in their unaffected relatives. The presence of circulating endotoxins could be due, at least in part, to the impaired natural immunity in either patients with ulcerative colitis or in their first degree unaffected relatives. Lactoferrin is an iron-binding glycoprotein, which binds to the lipid A region of lipopolysaccharide with a high affinity and this interaction prevents the binding of lipopolysaccharide to CD14, thus inhibiting the release of proinflammatory cytokines. Therefore, based on the possible pathogenic role exerted by endotoxins in ulcerative colitis, lactoferrin may deserve attention as a possible therapeutical agent in experimental models of Inflammatory Bowel Disease.
Current Pharmaceutical Design
Title: Immune Abnormalities and Endotoxemia in Patients with Ulcerative Colitis and in Their First Degree Relatives: Attempts at Neutralizing Endotoxin- Mediated Effects
Volume: 9 Issue: 24
Author(s): L. Amati, L. Caradonna, G. Leandro, T. Magrone, M. Minenna, G. Faleo, N. M. Pellegrino, E. Jirillo and D. Caccavo
Affiliation:
Abstract: Proinflammatory cytokines released from monocytes / macrophages, in particular tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and IL-8 seem to play an important role in Inflammatory Bowel Disease (ulcerative colitis and Crohns disease). Endotoxins or lipopolysaccharides, derived from the outer membrane of Gram-negative bacteria interact with CD14 on surface membrane of macrophages, thus triggering a signal cascade, which leads to the production and release of proinflammatory cytokines, particularly TNF-α. Therefore, in IBD, lipopolysaccharides could play a pathogenic role. In this respect, plasma endotoxins have been demonstrated in a not negligible percentage of patients with ulcerative colitis and in their unaffected relatives. The presence of circulating endotoxins could be due, at least in part, to the impaired natural immunity in either patients with ulcerative colitis or in their first degree unaffected relatives. Lactoferrin is an iron-binding glycoprotein, which binds to the lipid A region of lipopolysaccharide with a high affinity and this interaction prevents the binding of lipopolysaccharide to CD14, thus inhibiting the release of proinflammatory cytokines. Therefore, based on the possible pathogenic role exerted by endotoxins in ulcerative colitis, lactoferrin may deserve attention as a possible therapeutical agent in experimental models of Inflammatory Bowel Disease.
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Cite this article as:
Amati L., Caradonna L., Leandro G., Magrone T., Minenna M., Faleo G., Pellegrino M. N., Jirillo E. and Caccavo D., Immune Abnormalities and Endotoxemia in Patients with Ulcerative Colitis and in Their First Degree Relatives: Attempts at Neutralizing Endotoxin- Mediated Effects, Current Pharmaceutical Design 2003; 9 (24) . https://dx.doi.org/10.2174/1381612033454324
DOI https://dx.doi.org/10.2174/1381612033454324 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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