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Isomaltitol exacerbates neutrophilia but reduces eosinophilia: New insights into the Sephadex model of lung inflammation
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
Division of Clinical Chemistry, Kalmar County Hospital, Kalmar, Sweden.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
2011 (Engelska)Ingår i: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 154, nr 4, s. 286-294Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Karger , 2011. Vol. 154, nr 4, s. 286-294
Nyckelord [en]
Isomaltitol, Sephadex, inflammation, oedema, asthma
Nationell ämneskategori
Lungmedicin och allergi Farmakologi och toxikologi
Identifikatorer
URN: urn:nbn:se:liu:diva-19097DOI: 10.1159/000321820ISI: 000288529200003OAI: oai:DiVA.org:liu-19097DiVA, id: diva2:223271
Anmärkning
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. http://dx.doi.org/10.1159/000321820 Copyright: S. Karger AG http://www.karger.com/ Tillgänglig från: 2009-06-11 Skapad: 2009-06-11 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
Ingår i avhandling
1. Uridine, 4-thiouridine and isomaltitol in an asthma-like model: Anti-inflammatory and modulating effects
Öppna denna publikation i ny flik eller fönster >>Uridine, 4-thiouridine and isomaltitol in an asthma-like model: Anti-inflammatory and modulating effects
2009 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2009. s. 140
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1137
Nyckelord
Uridine, asthma, 4-thiouridine, isomaltitol, isomalt, inflammation, eosinophilia, Sephadex, animal model, rat
Nationell ämneskategori
Farmakologi och toxikologi Medicin och hälsovetenskap Lungmedicin och allergi
Identifikatorer
urn:nbn:se:liu:diva-19122 (URN)978-91-7393-596-8 (ISBN)
Disputation
2009-08-28, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 13:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2009-06-16 Skapad: 2009-06-12 Senast uppdaterad: 2020-02-26Bibliografiskt granskad

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