Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect.
Animals
Administration, Inhalation
Asthma
/ immunology
Bronchoalveolar Lavage Fluid
/ chemistry
Cytokines
/ immunology
Dinucleoside Phosphates
/ administration & dosage
Disease Models, Animal
Dose-Response Relationship, Drug
Double-Blind Method
Horse Diseases
/ immunology
Horses
Immunomodulation
/ immunology
Oligodeoxyribonucleotides
/ administration & dosage
Prospective Studies
Treatment Outcome
allergic asthma
extrinsic asthma
heaves
inhalation
neutrophilic asthma
Journal
Immunity, inflammation and disease
ISSN: 2050-4527
Titre abrégé: Immun Inflamm Dis
Pays: England
ID NLM: 101635460
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
09
11
2018
revised:
08
04
2019
accepted:
12
04
2019
pubmed:
30
5
2019
medline:
16
1
2020
entrez:
30
5
2019
Statut:
ppublish
Résumé
Equine asthma represents a naturally occurring animal model for human allergic neutrophilic asthma. Inhalative nanoparticle-bound cytosine-phosphate-guanosine (CpG-GNP) immunotherapy, independent of specific allergens, has already shown promising clinical and immunological results in previous studies and offers the possibility to treat the underlying cause of the disease. This study analyses the relationship between dose and response, and evaluates a possible long-term effect. In the prospective, randomised, double-blind clinical field study, 29 horses suffering from equine asthma received 10 inhalation treatments with either 187.5 µg CpG-GNP (CpG single dose [CpGsd]; n = 11), 375 µg CpG-GNP double dose (CpG double dose [CpGdd]; n = 9) (q48h for 20 days) or 1600 µg beclomethasone (n = 9) (q24h for 10 days). Each horse was examined three times: before the treatment (I), immediately after the 10 inhalations (II), and 8 weeks after the final inhalation (III). The three groups were compared according to clinical and laboratory parameters. The study examined the sustainability of the long-term effect of the treatment after 8 weeks, as well as the tolerability of the formula as a double dose. The CpGsd resulted in a significant improvement in 82% of the parameters, the CpGdd in 72%. In the long-term evaluation, the CpGsd showed a significant improvement in 100% of the parameters in comparison to the initial values, the CpGdd in 67%. On the immunological level, the bronchoalveolar lavage revealed a significant reduction of IL-4, IL-8, and interferon-γ. Both CpG groups displayed significant improvements in clinical and laboratory parameters, especially regarding the long-term effect of CpGsd. Doubling the CpG dose did not result in any improvement in comparison to the original single dose. On the immunological level, an anti-inflammatory, as well as an immunomodulatory effect, apart from a Th2-dominated immune response, could be observed. This immunomodulatory inhalation treatment could indicate a new possibility for human allergic asthma therapy.
Identifiants
pubmed: 31141308
doi: 10.1002/iid3.252
pmc: PMC6688086
doi:
Substances chimiques
cytidylyl-3'-5'-guanosine
2382-65-2
Cytokines
0
Dinucleoside Phosphates
0
Oligodeoxyribonucleotides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
130-149Informations de copyright
© 2019 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
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