Recurrent airway obstruction in horses - an allergic inflammation: a review

Abstract

Recurrent airway obstruction (RAO), also known as heaves, is a debilitating and incurable disease of the equine airway. Affected horses develop bronchoconstriction and neutrophilic airway inflammation as a result of exposure to specific airborne irritants and allergens such as hay mould and barn dust. Clinical signs of RAO include exercise intolerance, coughing, nostril flare and abdominal push related to respiratory effort. Evidence suggests that both the innate and acquired immune response contribute to the activation of inflammatory cells resulting in type I hypersensitivity and type III hypersensitivity reactions with an increased expression of Th1-and Th2-cytokines, chemokines, adhesion molecules, receptors and release of reactive oxygen species (ROS). The regulation of inflammatory gene expression in RAO-affected horses is dependent on the binding of transcription factors such as Nuclear factor-(kappa)B (NF-kB), activator protein-1 (AP-1) and the cyclic AMP response element binding protein (CREB) to the promoter region of target genes. In chronic disease an increased number of mucous-producing cells and increased amounts of stored mucins are observed in conjunction with other characteristics of airway tissue remodelling. In this review the findings related to the inflammatory and immunologic response in RAO-affected horses will be presented, and this information will be integrated into existing concepts of immunopathologic mechanisms. Keywords: RAO; horses; cytokines; immune response; airway inflammationList of abbreviations AP-1 = activator protein-1; BALF = bronchoalveolar lavage fluid; CREB = cyclic AMP response element binding prote; eCLCA1 = calcium-activated chloride channels; NF-kB = nuclear factor-(kappa)B; RAO = recurrent airway obstruction; ROS = reactive oxygen species; TLRs = Toll-like receptors

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

“…An excessive pro-allergic Th2 immune response cannot be documented in all cases of equine asthma [33], probably due to individual factors such as exacerbation phase, duration of the disease, genetic, and exogenous trigger factors and allergen load [34]. The initial concentration of IL-4 in the horses varied greatly.…”

Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma

“…Previous studies investigating the type of response in RAO have found conflicting results. The time point of sampling and the duration of stimulation, respectively, may influence results [ 9 ]. In the present study, we observed downregulation of both Th1 type ( IFNG ) and Th2-type cytokines ( IL4 , IL13 ) in RAO cells stimulated with HDE.…”

“…Apart from humans, allergic asthmatic conditions occur naturally only in cats and horses [ 8 ]. The asthma-like disease in horses is called recurrent airway obstruction (RAO), which is a debilitating and incurable respiratory disease affecting stabled mature horses worldwide [ 9 – 11 ]. RAO-affected horses develop marked airway obstruction due to bronchospasm, inflammation, mucus accumulation and remodelling resulting in severe clinical signs such as coughing, respiratory distress and increased breathing effort during periods of exacerbation, which are triggered by hypersensitivity reactions to allergens and irritants mainly from hay dust [ 11 – 14 ].…”

“…Gene expression studies may potentially highlight genes that play a key role in the response to RAO-related antigens. Some studies showed contradictory results regarding the involvement of cytokines characteristic for Th1 or Th2 type immune response and it has been suggested that cytokine profiles reflecting both types of Th responses are observed at different time-points after antigen challenge [ 9 ]. In addition, an increased expression level of IL17 , which is characteristic for Th17 cells, was shown to be associated with RAO [ 19 ].…”

Nanoparticulate CpG Immunotherapy in RAO‐Affected Horses: Phase I and IIa Study

“…3,7,8 Clinical variables include cholinergic bronchospasm, hypercrinia and dyscrinia, nasal discharge, coughing, airway neutrophilia, airway remodeling, and edema, resulting in poor performance. 1,8,9 Cytosine-phosphate-guanosine-oligodeoxynucleotide (CpG-ODN) has been identified as a molecule that directs the immune system toward a cell-mediated Th1 pathway, away from the pro-allergic humoral Th2 line response, described as a Th2/Th1-shift. 3,10,11 Unmethylated CpG-ODN molecules exist naturally in prokaryotic viral and bacterial DNA and stimulate the mammalian immune system, via the Th1 pathway, against infectious agents.…”