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Immunity, inflammation and disease2019; 7(3); 130-149; doi: 10.1002/iid3.252

Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect.

Abstract: 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.
© 2019 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
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Publication Date: 2019-05-29 PubMed ID: 31141308PubMed Central: PMC6688086DOI: 10.1002/iid3.252Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores the effects and long-term benefits of a nanoparticle-bound immunotherapy on horses suffering from equine asthma, which serves as an animal model for human allergic asthma. Surprisingly, increasing the dose of the treatment did not yield better results, and the single dose therapy successfully improved asthmatic symptoms in horses and reduced certain inflammation markers.

Study Overview

  • The research utilises equine asthma – a condition in horses that closely resembles human allergic asthma – as an animal model to test an immunotherapy treatment.
  • The treatment being tested involves inhalable nanoparticles bound with cytosine-phosphate-guanosine (CpG-GNP), which has already shown promising results in treating the root cause of equine asthma.
  • The primary goals of the study were to assess the relationship between the dosage of CpG-GNP and its effectiveness, and to observe any potential long-term effects of the treatment.
  • The study was designed as a prospective, randomised, double-blind clinical field trial, conducted on 29 horses.

Methodology and Findings

  • The horses were randomly split into three groups. Two groups received different doses of CpG-GNP (group 1: single dose, group 2: double dose), while the third group was treated beclomethasone, a standard medication for asthma.
  • The horses were evaluated before treatment, immediately after treatment and 8 weeks after treatment, and the three groups were compared based on clinical and laboratory parameters.
  • The single dose CpG-GNP group presented a significant improvement in 82% of monitored parameters, versus 72% in the double dose group. The long-term follow-up showed an even more remarkable result: 100% improvement in the single dose CpG-GNP group, versus 67% in the double dose group.
  • The bronchoalveolar lavage results indicated a significant reduction in several inflammatory cytokines (IL-4, IL-8, and interferon-γ).

Conclusions and Implications

  • The researchers concluded that the CpG-GNP treatment led to major improvements in clinical and laboratory parameters, particularly in regards to its long-term effects.
  • Interestingly, doubling the dose did not result in increased efficacy relative to the original single dose.
  • The treatment demonstrated an anti-inflammatory and immunomodulatory response, attenuating an otherwise predominantly Th2-immune response, which characterizes allergic asthma.
  • This innovative immunomodulatory treatment paves the way for potential new approaches in treating human allergic asthma.

Cite This Article

APA
Klier J, Bartl C, Geuder S, Geh KJ, Reese S, Goehring LS, Winter G, Gehlen H. (2019). Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect. Immun Inflamm Dis, 7(3), 130-149. https://doi.org/10.1002/iid3.252

Publication

Immunity, inflammation and disease
ISSN: 2050-4527
NlmUniqueID: 101635460
Country: England
Language: English
Volume: 7
Issue: 3
Pages: 130-149

Researcher Affiliations

Klier, John
  • Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig-Maximilians-University, Munich, Germany.
Bartl, Carolin
  • Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig-Maximilians-University, Munich, Germany.
  • Department of Veterinary Medicine, Equine Clinic, Surgery and Radiology, Free University of Berlin, Berlin, Germany.
Geuder, Sabine
  • Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig-Maximilians-University, Munich, Germany.
Geh, Katharina J
  • Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Munich, Germany.
Reese, Sven
  • Department of Veterinary Medicine, Equine Clinic, Surgery and Radiology, Free University of Berlin, Berlin, Germany.
Goehring, Lutz S
  • Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig-Maximilians-University, Munich, Germany.
Winter, Gerhard
  • Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Munich, Germany.
Gehlen, Heidrun
  • Department of Veterinary Medicine, Equine Clinic, Surgery and Radiology, Free University of Berlin, Berlin, Germany.

MeSH Terms

  • Administration, Inhalation
  • Animals
  • Asthma / immunology
  • Asthma / therapy
  • Asthma / veterinary
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dinucleoside Phosphates / administration & dosage
  • Dinucleoside Phosphates / immunology
  • Dinucleoside Phosphates / therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Horse Diseases / immunology
  • Horse Diseases / therapy
  • Horses
  • Humans
  • Immunomodulation / immunology
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / immunology
  • Oligodeoxyribonucleotides / therapeutic use
  • Prospective Studies
  • Treatment Outcome

Conflict of Interest Statement

The authors declare no competing financial interests. The study was conducted at the Equine Clinic, Centre for Clinical Veterinary Medicine, LMU Munich, Germany. Part of the lab work was performed by CB and JK in the lab of the Institute for Animal Welfare, Ethology, Animal Hygiene and Animal Husbandry, Faculty of Veterinary Medicine, Department of Veterinary Science, Ludwig‐Maximilians‐University, Munich. An abstract of this study was presented in part at the 2016 British Equine Veterinary Association (BEVA) Congress, Birmingham, England.

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Citations

This article has been cited 6 times.
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