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Anti-inflammatory effects of exogenous uridine in an animal model of lung inflammation.
Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Division of Clinical Chemistry, Kalmar County Hospital, 391 85 Kalmar, Sweden.
Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
2007 (English)In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 7, no 8, 1025-1032 p.Article in journal (Refereed) Published
Abstract [en]

Nucleosides like adenosine, uridine and their nucleotide derivatives (e.g. ATP and UTP) play important roles in many cellular functions, sometimes by acting as signalling molecules through binding to specific P2 nucleotide receptors. P2 receptors are subdivided into P2X and P2Y subfamilies, the latter of which are G-protein coupled receptors. P2Y receptors and nucleoside transporters have been detected in human and rat lungs, where they mediate effects of interest in airway diseases. The aim of this study was to investigate whether uridine has any anti-inflammatory properties in an asthma-like animal model of lung inflammation.

The Sephadex-induced lung inflammation model in Sprague-Dawley rats was chosen mainly due to its localised inflammatory response and uridine's limited oral bioavailability. The dextran beads, with or without the addition of uridine, were instilled intratracheally into the lungs, which were excised and examined after 24 h.

Sephadex alone led to massive oedema and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. Uridine reduced both the oedema and the infiltration of leukocytes significantly, measured as lung wet weight and leukocyte counts in bronchoalveolar lavage fluid, respectively. Uridine appeared to affect the tumour necrosis factor (TNF) levels, although this could not be statistically confirmed due to large variations within the Sephadex control group.

We conclude that uridine has anti-inflammatory effects, and that the exact mechanism(s) of action requires further study.

Place, publisher, year, edition, pages
2007. Vol. 7, no 8, 1025-1032 p.
Keyword [en]
Asthma, Inflammation, Leukocytes, Sephadex, Tumour necrosis factor, Uridine
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-19095DOI: 10.1016/j.intimp.2007.03.008PubMedID: 17570319OAI: diva2:223272
Available from: 2009-06-11 Created: 2009-06-11 Last updated: 2010-06-28Bibliographically approved
In thesis
1. Uridine, 4-thiouridine and isomaltitol in an asthma-like model: Anti-inflammatory and modulating effects
Open this publication in new window or tab >>Uridine, 4-thiouridine and isomaltitol in an asthma-like model: Anti-inflammatory and modulating effects
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In chronic inflammatory diseases like asthma or rheumatoid arthritis, erroneous and exaggerated accumulation of leukocytes in a tissue inadvertently causes the body harm. Several efficient anti-inflammatory drugs exist, for example corticosteroids and cyclo-oxygenase inhibitors. However, these drugs have potent and diverse effects and often act by inhibiting events subsequent to initiation of the inflammatory response, leading to more or less severe side-effects, especially when used in high doses for long periods of time. For this reason, strategies aimed at early inhibition of recruitment and activation of leukocytes have been suggested as safer and more specific approaches to reduce inflammation.

Leukocyte adhesion to activated endothelium is a prerequisite to the following activation and extravasation, and takes place in the initial phase of inflammation. By using a model that allows leukocytes to adhere to tumour necrosis factor (TNF)-activated endothelial cells, thus mimicking aspects of an inflammatory reaction, we found that uridine, 4-thiouridine and isomaltitol could all reduce adhesion. This suggested that they may have anti-inflammatory potential.

We therefore tried the three substances in a Sephadex-induced lung inflammation model and found that uridine and 4-thiouridine have several anti-inflammatory effects, such as being able to reduce leukocyte accumulation, decrease TNF protein levels and partly inhibit the oedema induced by Sephadex. Isomaltitol turned out to have immunomodulating, rather than anti-inflammatory, effects, which could be of interest in diseases where inadequate inflammatory responses are a problem.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. 140 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1137
Uridine, asthma, 4-thiouridine, isomaltitol, isomalt, inflammation, eosinophilia, Sephadex, animal model, rat
National Category
Pharmacology and Toxicology Medical and Health Sciences Respiratory Medicine and Allergy
urn:nbn:se:liu:diva-19122 (URN)978-91-7393-596-8 (ISBN)
Public defence
2009-08-28, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 13:00 (Swedish)
Available from: 2009-06-16 Created: 2009-06-12 Last updated: 2012-05-09Bibliographically approved

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