Asymmetrical Pulmonary Cytokine Profiles Are Linked to Bronchoalveolar Lavage Fluid Cytology of Horses With Mild Airway Neutrophilia

Abstract

Few data on cytokine profiles in bronchoalveolar lavage fluid (BALF) are available for racehorses with mild/moderate equine asthma (EA); cytological diagnosis being most frequently made from only one lung. The purpose of the study was to compare cytokine mRNA expressions and protein concentrations in BALF from both lungs. As part of a larger study, 250 ml saline was randomly instilled in one lung and 500 ml in the contralateral lung of 30 clinically healthy Standardbred racehorses. This procedure was repeated 72 h later, inversing the volume per lung. Cytological cutoff values for diagnosis of mild EA was neutrophil proportions > 10% when instilling 250 ml. Eleven horses that exhibited unilateral mild inflammatory cytology [i.e., normal cytology (<10% neutrophils) in the other lung] were enrolled. Protein concentrations were not significantly different between lungs, for any of the investigated cytokines. Relative mRNA expression of IL-1β (3.887 ± 0.929) and IL-10 (3.225 ± 0.516) were significantly higher in BALF from mild inflammatory lungs when compared with non-inflammatory ones (1.408 ± 0.337 and 1.488 ± 0.420, respectively); and also significantly correlated with neutrophil proportions (R = 0.45 and R = 0.58, respectively). These findings suggest that specific inflammatory response and/or regulation locally occurs within the lower airways.

Predictive value of chemokines (CCL 2) in bronchoalveolar lavage fluid for refractory mycoplasma pneumonia in children

“…Studies suggest that excessive immune response is involved in the formation of RMPP, and CCL2 is involved in the immune response. Hue Erika et al [ 37 ] found in an animal experiment that the level of cytokines in the bronchoalveolar lavage fluid (BALF) of the affected side was significantly higher than that of the healthy side. It has a higher predictive value than CRP and LDH in predicting the occurrence of RMPP.…”

“…Compared with serum markers, the changes of biomarkers in BALF have higher specificity and sensitivity, and can indicate the progression of lung diseases earlier and more accurately. In an animal study, Hue Erika et al [ 19 ] found that the cytokine levels in bronchoalveolar lavage fluid (BALF) of the affected side were significantly higher than those in the healthy side, possibly due to further lung injury caused by excessive activation of immune cells. The strong local inflammatory response of MPP suggests that the chemokines in BALF may be more meaningful for the prediction of RMPP.…”

Asthma: The Use of Animal Models and Their Translational Utility

“…Unlike human asthma, the term ‘severe’ for EA is used to describe a greater degree of lower airway inflammation and severity of clinical signs but does not necessarily mean the asthma is difficult to manage or treat. Equine asthma is a chronic inflammatory lung disease with characteristics similar to human asthma, including enhanced bronchial reactivity; chronic, partially reversible airflow obstruction; pulmonary remodeling; lower airway inflammation [ 224 , 225 , 226 ]. Equine asthma prevalence is not clearly defined, but some studies suggest that up to 80% of horses may have mEA and up to 17% may have sEA [ 227 , 228 , 229 , 230 , 231 ].…”

“…While mouse models of neutrophilic asthma are now available [ 270 ], and have been used to identify novel biomarkers and therapeutic approaches [ 271 , 272 ], horses are another potentially useful translational model for this important asthma endotype. Like asthma in humans, sEA is a chronic disease that leads to structural changes in the lung that mirror changes in humans with asthma [ 225 , 273 ]. With environmental management, asthmatic horses can be maintained in remission and exacerbation can be induced when needed by feeding dusty/moldy hay or nebulizing hay dust extract (HDE).…”

Initial investigation of molecular phenotypes of airway mast cells and cytokine profiles in equine asthma

“…In studies of asthmatic horses, these endotypes have been identified in both EA phenotypes, mEA and sEA, suggesting classification systems other than mEA and sEA may be needed to describe underlying disease immunopathology (8). The cytokine profiles of mEA and sEA, either at the protein or mRNA level, may support a type 1, type 2, type 17, or mixed immune response, depending on the study (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Inconsistencies in reported cytokine profiles and subcategorizing EA based on clinical severity rather than immune characteristics of the disease have limited ability to fully describe the pathogenesis of EA and establish clinically relevant disease categories, which ultimately limits diagnostic, treatment, and management abilities.…”