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

Abstract

Introduction 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. Methods 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. Results 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. Conclusion 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.

Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

“…Of these, the majority of MSC studies have been carried out with MSCs isolated from horses, driven by the high demand of horse owners for innovative regenerative therapies, primarily geared toward the treatment of musculoskeletal injuries. Horses are well-characterized as models for specific human diseases, most notably orthopedic injuries such as OA ( McCoy, 2015 ), but also skin wounds ( Harman et al, 2019 ), and respiratory diseases ( Klier et al, 2019 ), all of which have the potential to be managed by treatment with MSC secreted factors ( De Schauwer et al, 2013 ) ( Figure 3 ). Pigs have long been considered valuable preclinical models for a variety of human therapies, as exemplified by the use of pig organs that are quite similar to those of humans in terms of size, morphology, and function ( Roth and Tuggle, 2015 ).…”

Glucocorticoid treatment in horses with asthma: A narrative review

“…29 The effects of GC on arterial blood gas are conflicting. [30][31][32][33][34] The lack of a control group 33,34 or the combination of GC administration with environmental modifications and bronchodilators, 30,31 complicated the interpretation of the results.…”

“…However, this study lacked a placebo control group and the unusual persistence of beneficial effects suggests that the antigenic exposure was not stable, despite effort to do so. 34 The reduction of airway obstruction by beclomethasone is supported by in vitro experiments in which precision‐cut lung slices from horses without respiratory disease were studied. The bronchoconstriction induced by leukotriene C 4 is attenuated by beclomethasone and the rapid onset of action (<30 minutes) suggests a nongenomic mechanism of action.…”

Horses as a Crucial Part of One Health

“…As an animal model, horses were used in the research of Hepatitis C, since the virus displays great similarities to the equine hepacivirus [59,60]. Furthermore, horses were employed as a model for respiratory diseases (human allergic neutrophilic asthma) [61], orthopedic problems (focal articular cartilage injuries) [62,63], and in defining the causes of depression as an ethological animal model [64].…”