A1 Refereed original research article in a scientific journal
A novel glycocluster molecule prevents timothy-induced allergic airway inflammation in mice
Authors: Lehto M, Wolff H, Leino R, Alenius H, Savolainen J
Publisher: WILEY
Publication year: 2018
Journal: Allergy
Journal name in source: ALLERGY
Journal acronym: ALLERGY
Volume: 73
Issue: 8
First page : 1700
Last page: 1706
Number of pages: 7
ISSN: 0105-4538
eISSN: 1398-9995
DOI: https://doi.org/10.1111/all.13419
Abstract
BackgroundAllergen-specific immunotherapy (SIT) effectively alleviates type I allergic diseases characterized by T helper (Th)2-type immunity. Our recent studies have shown that a synthetic trivalent glycocluster, triacedimannose (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was to compare TADM with two well-known adjuvants, unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG) and monophosphoryl lipidA (MPLA) in a grass allergen-induced chronic allergic inflammation model in mice.MethodsFemale BALB/c mice were intranasally sensitized with 50L of timothy grass pollen extract (TE) twice a week for a period of 15weeks. Therapeutic intranasal treatments were then performed once a week after the tenth intranasal TE instillation using TADM (10 or 25g/50L), CpG-ODN (20g/50L) or MPLA (2g/50L). Groups of 9-10 animals per treatment were killed 24hours after the last timothy dosage. Blood, bronchoalveolar lavage (BAL) fluids and lung biopsies were taken for subsequent analysis.ResultsWhen mice were repeatedly exposed to TE for 15weeks, the number of eosinophils and lymphocytes increased in the BAL fluids. The eosinophil and lymphocyte counts decreased dose-dependently and were practically abolished in the mice treated with TADM. Treatments with MPLA or CpG significantly increased the numberof neutrophils, while CpG nonsignificantly decreased eosinophilia compared to timothy exposure.ConclusionsA novel synthetic glycocluster molecule inhibited the development of grass-induced eosinophilic pulmonary inflammation in mice when administrated in the airways. This compound could be a candidate to be used either as an adjuvant in SIT or as a topical anti-inflammatory treatment.
BackgroundAllergen-specific immunotherapy (SIT) effectively alleviates type I allergic diseases characterized by T helper (Th)2-type immunity. Our recent studies have shown that a synthetic trivalent glycocluster, triacedimannose (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was to compare TADM with two well-known adjuvants, unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG) and monophosphoryl lipidA (MPLA) in a grass allergen-induced chronic allergic inflammation model in mice.MethodsFemale BALB/c mice were intranasally sensitized with 50L of timothy grass pollen extract (TE) twice a week for a period of 15weeks. Therapeutic intranasal treatments were then performed once a week after the tenth intranasal TE instillation using TADM (10 or 25g/50L), CpG-ODN (20g/50L) or MPLA (2g/50L). Groups of 9-10 animals per treatment were killed 24hours after the last timothy dosage. Blood, bronchoalveolar lavage (BAL) fluids and lung biopsies were taken for subsequent analysis.ResultsWhen mice were repeatedly exposed to TE for 15weeks, the number of eosinophils and lymphocytes increased in the BAL fluids. The eosinophil and lymphocyte counts decreased dose-dependently and were practically abolished in the mice treated with TADM. Treatments with MPLA or CpG significantly increased the numberof neutrophils, while CpG nonsignificantly decreased eosinophilia compared to timothy exposure.ConclusionsA novel synthetic glycocluster molecule inhibited the development of grass-induced eosinophilic pulmonary inflammation in mice when administrated in the airways. This compound could be a candidate to be used either as an adjuvant in SIT or as a topical anti-inflammatory treatment.
UTU Research Portal