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Isomaltitol exacerbates neutrophilia but reduces eosinophilia: New insights into the Sephadex model of lung inflammation
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
2011 (English)In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 154, no 4, 286-294 p.Article in journal (Refereed) Published
Abstract [en]

We have previously examined isomaltitol in an in vitro static adhesion assay between isolated granulocytes and cultured human umbilical cord vein cells and were interested in investigating whether the potentially anti-inflammatory effects observed there could be reproduced in vivo. The Sephadex-induced lung inflammation model was considered a suitable model due to the significant changes in global inflammatory endpoints, like oedema and leukocyte migration, usually seen upon provocation with Sephadex.

Male Sprague-Dawley rats were instilled intratracheally with Sephadex (5 mg/ml), vehicle (0.9% NaCl), isomaltitol (50 mg/ml) or a combination of isomaltitol and Sephadex. After 24 h, the lungs were weighed to measure oedema and preserved for histology. Bronchoalveolar lavage fluid was used for analysis of tumour necrosis factor, cysteinyl leukotrienes, and differential and total leukocyte counts. In addition, blood differential counts and thymus weights were analysed.

Contrary to what we expected from in vitro experiments, differential counts showed that isomaltitol increased the neutrophil component while decreasing the eosinophilia. Isomaltitol thus asserted a modulatory role on the usually eosinophil-dominated Sephadex-induced cell profile. Isomaltitol alone also increased several inflammatory parameters, including oedema and cysteinyl leukotrienes, and generally aggravated total inflammation in combination with Sephadex. Although the mechanisms were not investigated in this study, the effects could relate to a combination of isomaltitol's osmotic and structure-specific properties.

Our results indicate that isomaltitol can modulate the inflammatory response induced by Sephadex instillation in addition to have pro-inflammatory effects on it its own, and may therefore provide new insights into the mechanisms of this widely used animal model. Sugar alcohols similar to isomaltitol have already been used to aid mucus clearance in cystic fibrosis patients, and it is possible that isomaltitol could also be used for this purpose.

Place, publisher, year, edition, pages
Karger , 2011. Vol. 154, no 4, 286-294 p.
Keyword [en]
Isomaltitol, Sephadex, inflammation, oedema, asthma
National Category
Respiratory Medicine and Allergy Pharmacology and Toxicology
URN: urn:nbn:se:liu:diva-19097DOI: 10.1159/000321820ISI: 000288529200003OAI: diva2:223271
Original Publication: Chamilly Evaldsson, Ingvar Rydén and Srinivas Uppugunduri, Isomaltitol exacerbates neutrophilia but reduces eosinophilia: New insights into the Sephadex model of lung inflammation, 2011, International Archives of Allergy and Immunology, (154), 4, 286-294. Copyright: S. Karger AG Available from: 2009-06-11 Created: 2009-06-11 Last updated: 2011-04-19Bibliographically 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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