Time-dependent changes of cytokines mRNA in bronchoalveolar lavage fluid from symptomatic Recurrent Airway Obstruction-affected horses

Abstract

During an 18 day test, we measured the cytokine mRNA expression (Interleukin-1β , , Interferon-γ [IFN-γ], Tumor Necrosis Factor-α [TNF-α]) of cells from bronchoalveolar lavage fluid [BALF] in five horses previously diagnosed with RAO, before and during challenge exposure, and after the desensitization phase which involved dexamethasone treatment and environmental modification. Simultaneously, the same cytokine mRNA expression of cells from BALF in four asymptomatic RAO-affected horses maintained outdoors was analyzed. An evident respiratory distress was observed in the challenge group within 3 days, with a significant overexpression of IL-8 and TNF-α mRNA on the ninth day. The pharmacological and environmental desensitization provided a down regulation of all the cytokines. No statistical modification characterized the cytokine kinetics of the asymptomatic horses maintained outdoors. A comparison for each time point of the cytokines between the exposed and unexposed horses showed no significant differences. The study suggested that a standardized exposure protocol and sampling time in experimental studies of RAO is mandatory for a correct comparison of the results obtained by different Authors. However, the absence of significant changes between the exposed and unexposed horses could depend on the lack of the sample uniformity since the evolution of the disease represents a continuum from a healthy to a pathological condition.

Recurrent airway obstruction: A review

“…The proposed reasons for these contrasting results can only be hypothesised at this stage; however, they include the following: differences in sample collection time points in relation to either the time of challenge or the onset of clinical signs ; a unique equine pulmonary immunological response that fails to meet the current hypersensitivity subdivision definitions precisely; varied immunological mechanisms leading to a common disease phenotype or a mixed Th1/Th2 response . The latter 2 proposals may not be unexpected considering the fact that airborne organic dust, exposure to which constitutes the recognised method of disease induction and therefore subject categorisation into ‘susceptible’ and ‘nonsusceptible’, contains numerous proinflammatory agents (allergenic and nonallergenic), many of which probably have the ability to skew the ultimate cytokine and gene expression profile, dependent on their concentration relative to other dust components.…”

Comparative Pathology and Immunohistochemistry of Veterinary Species

“…In previous studies in humans, CD44 positive cells in gastric cell lines were associated with increased chemoresistance and invasiveness [66]. Additionally, CD44 positive gastric tumors were associated with larger tumor size, a lower grade of differentiation, tumor relapse, lymph node invasion, distant metastasis and reduced survival [63][64][65][66]. It seems that CD44 may represent an important biomarker and a promising therapeutic target in canine gastric carcinomas.…”

“…CD44 serves as a signaling platform, with transmembrane and cytoplasmic domains as a co-receptor for various types of cell surface receptors that modulate cell adhesion, migration, proliferation, differentiation and survival [63][64][65][66]. In humans, its role in the adaptive plasticity and survival of cancer cells in processes like epithelial to mesenchymal transition, invasion and metastasis has been widely studied [67,68].…”

Immunohistochemical Expression of Neurokinin-A and Interleukin-8 in the Bronchial Epithelium of Horses with Severe Equine Asthma Syndrome during Asymptomatic, Exacerbation, and Remission Phase

“…On the contrary, in the study by Pietra et al, 2011, although a significant overexpression of IL-8 and TNFα mRNA on BALF was observed in the group of treated horses, with a peak around the ninth day, a comparison between exposed and unexposed horses does not reveal significant differences [ 64 ]. According to the authors, this evidence could depend on the loss of uniformity of the sample, since the evolution of the pathology represents a continuum from healthy to pathological conditions.…”

“…Studies on horses with severe equine respiratory syndrome have revealed an increase in the gene expression of the pro-inflammatory cytokine IL-8 in bronchoalveolar cells [ 19 , 38 , 40 , 52 , 58 , 59 ], as well as an increase in IL-8 protein concentration in BALF [ 19 , 37 , 38 , 40 , 60 , 61 , 62 , 63 , 64 , 65 ].…”