A novel glycocluster molecule prevents timothy-induced allergic airway inflammation in mice.

Abstract

BACKGROUND:

Allergen-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 lipid A (MPLA) in a grass allergen-induced chronic allergic inflammation model in mice.

METHODS:

Female BALB/c mice were intranasally sensitized with 50 μL of timothy grass pollen extract (TE) twice a week for a period of 15 weeks. Therapeutic intranasal treatments were then performed once a week after the tenth intranasal TE instillation using TADM (10 or 25 μg/50 μL), CpG-ODN (20 μg/50 μL) or MPLA (2 μg/50 μL). Groups of 9-10 animals per treatment were killed 24 hours after the last timothy dosage. Blood, bronchoalveolar lavage (BAL) fluids and lung biopsies were taken for subsequent analysis.

RESULTS:

When mice were repeatedly exposed to TE for 15 weeks, 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 numbers of neutrophils, while CpG nonsignificantly decreased eosinophilia compared to timothy exposure.

CONCLUSIONS:

A 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.

• Authors: M Lehto, H Wolff, R Leino, H Alenius, J Savolainen
• Journal: Allergy (Allergy) Vol. 73 Issue 8 Pg. 1700-1706 (Aug 2018) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 29377154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Chemical References

• Adjuvants, Immunologic
• Allergens
• CPG-oligonucleotide
• Disaccharides
• Lipid A
• Mannans
• Oligodeoxyribonucleotides
• Plant Extracts
• triacedimannose
• mannobiose
• monophosphoryl lipid A

Topics

• Adjuvants, Immunologic (therapeutic use)
• Allergens (immunology)
• Animals
• Bronchoalveolar Lavage Fluid (immunology)
• Desensitization, Immunologic
• Disaccharides
• Disease Models, Animal
• Eosinophils (drug effects, immunology)
• Female
• Hypersensitivity (prevention & control)
• Lipid A (analogs & derivatives, therapeutic use)
• Lymphocyte Count
• Mannans (chemical synthesis, therapeutic use)
• Mice
• Mice, Inbred BALB C
• Oligodeoxyribonucleotides (therapeutic use)
• Phleum (chemistry)
• Plant Extracts (administration & dosage, immunology)
• Pneumonia (chemically induced, pathology, prevention & control)
• Pollen (immunology)
• Statistics, Nonparametric