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Animals : an open access journal from MDPI2022; 12(16); 2087; doi: 10.3390/ani12162087

Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment.

Abstract: Severe equine asthma is the most common globally widespread non-infectious equine respiratory disease (together with its mild and moderate form), which is associated with exposure to hay dust and mold spores, has certain similarities to human asthma, and continues to represent a therapeutic problem. Immunomodulatory CpG-ODN, bound to gelatin nanoparticles as a drug delivery system, were successfully administered by inhalation to severe equine asthmatic patients in several studies. It was possible to demonstrate a significant, sustained, and allergen-independent one-to-eight-week improvement in key clinical parameters: the arterial partial pressure of oxygen, the quantity and viscosity of tracheal mucus, and neutrophilic inflammatory cells in the respiratory tracts of the severe equine asthmatic subjects. At the immunological level, an upregulation of the regulatory antiallergic and anti-inflammatory cytokine IL-10 as well as a downregulation of the proallergic IL-4 and proinflammatory IFN-γ in the respiratory tracts of the severe equine asthmatic patients were identified in the treatment groups. CD4 T lymphocytes in the respiratory tracts of the asthmatic horses were demonstrated to downregulate the mRNA expression of Tbet and IL-8. Concentrations of matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2 were significantly decreased directly after the treatment as well as six weeks post-treatment. This innovative therapeutic concept thus opens new perspectives in the treatment of severe equine asthma and possibly also that of human asthma.
Publication Date: 2022-08-16 PubMed ID: 36009677PubMed Central: PMC9405334DOI: 10.3390/ani12162087Google Scholar: Lookup
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Summary

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The research paper discusses the successful inhalative application of immunomodulatory CpG-ODN bound to gelatin nanoparticles in severe equine asthma treatment, and its potential for human asthma treatment.

Introduction & Rationale

  • Severe equine asthma is a prevalent non-infectious respiratory disease in horses, triggered by exposure to hay dust and mold spores. It shares many similarities with human asthma and presents challenges in terms of effective treatment.
  • The researchers aim to explore novel treatment methods for severe equine asthma, particularly focusing on immunotherapy involving immunomodulatory CpG-ODN (synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides) attached to gelatin nanoparticles, used as a drug delivery system.

Methodology

  • The researchers conducted several studies where they administered the immunomodulatory CpG-ODN bound to gelatin nanoparticles by inhalation to horses suffering from severe asthma.
  • The treatment’s efficacy is gauged by measuring key clinical parameters such as oxygen arterial partial pressure, quantity and viscosity of tracheal mucus, and the presence of neutrophilic inflammatory cells in the respiratory tracts of the subjects.

Findings

  • The treatment resulted in a significant and sustained improvement in the measured clinical parameters for a period of one to eight weeks, irrespective of allergen exposure.
  • The researchers found an upregulation of the regulatory antiallergic and anti-inflammatory cytokine IL-10 and a downregulation of the proallergic IL-4 and proinflammatory IFN-γ in the respiratory tracts of the asthmatic horses, suggesting the treatment had a beneficial impact on the immune responses associated with the disease.
  • CD4 T lymphocytes in the respiratory tracts of the horses showed a decrease in the expression of Tbet and IL-8 mRNA, two signals related to inflammation and immune response.
  • The concentrations of matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2 significantly decreased immediately after the treatment and remained lower even six weeks after the treatment.

Implication

  • This novel treatment approach to severe equine asthma opens up new possibilities in the field. The success of this inhalative immunotherapy also signifies its potential applicability in human asthma treatment, given the shared characteristics between the two diseases.

Cite This Article

APA
Klier J, Fuchs S, Winter G, Gehlen H. (2022). Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment. Animals (Basel), 12(16), 2087. https://doi.org/10.3390/ani12162087

Publication

ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 12
Issue: 16
PII: 2087

Researcher Affiliations

Klier, John
  • Equine Clinic, Centre for Clinical Veterinary Medicine, Ludwig-Maximilians-University, 85764 Oberschleißheim, Germany.
Fuchs, Sebastian
  • Pharmaceutical Technology and Biopharmaceutics, Faculty of Chemistry and Pharmacy, Ludwig-Maximilians-University, 81377 Munich, Germany.
Winter, Gerhard
  • Pharmaceutical Technology and Biopharmaceutics, Faculty of Chemistry and Pharmacy, Ludwig-Maximilians-University, 81377 Munich, Germany.
Gehlen, Heidrun
  • Equine Clinic, Surgery and Radiology, Department of Veterinary Medicine, Free University of Berlin, 14163 Berlin, Germany.

Conflict of Interest Statement

The authors declare no competing financial interest.

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