Isomaltitol exacerbates neutrophilia but reduces eosinophilia : New insights into the Sephadex model of lung inflammation

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Isomaltitol

Sephadex

inflammation

oedema

asthma

Lung diseases

Lungsjukdomar

Pharmaceutical pharmacology

Farmaceutisk farmakologi

Publikations- och innehållstyp

ref (ämneskategori)

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