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  • Author or Editor: Laurel J. Gershwin x
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Abstract

Objective—To evaluate the effect of infection with bovine respiratory syncytial virus (BRSV) on clearance of inhaled antigens from the lungs of calves.

Animals—Eleven 6- to 8-week-old Holstein bull calves.

Procedures—Aerosolized 99mtechnetium (99mTc)-labeled diethylene triamine pentacetate (DTPA; 3 calves), commonly used to measure integrity of the pulmonary epithelium, and 99mTc-labeled ovalbumin (OA; 8 calves), commonly used as a prototype allergen, were used to evaluate pulmonary clearance before, during, and after experimentally induced infection with BRSV or sham inoculation with BRSV. Uptake in plasma (6 calves) and lung-efferent lymph (1 calf) was examined.

Results—Clearance of 99mTc-DTPA was significantly increased during BRSV infection; clearance of 99mTc-OA was decreased on day 7 after inoculation. Clearance time was correlated with severity of clinical disease, and amounts of 99mTc-OA in plasma and lymph were inversely correlated with clearance time. Minimum amounts of 99mTc-OA were detected at time points when pulmonary clearance of 99mTc-OA was most delayed.

Conclusions and Clinical Relevance—BRSV caused infection of the respiratory tract with peak signs of clinical disease at 7 or 8 days after inoculation. Concurrently, there was a diminished ability to move inhaled protein antigen out of the lungs. Prolonged exposure to inhaled antigens during BRSV infection may enhance antigen presentation with consequent allergic sensitization and development of chronic inflammatory lung disease.

Impact for Human Medicine—Infection of humans with respiratory syncytial virus early after birth is associated with subsequent development of allergic asthma. Results for BRSV infection in these calves suggested a supportive mechanism for this scenario.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess IgE response and cytokine gene expressions in pulmonary lymph collected from bovine respiratory syncytial virus (BRSV)-infected calves after ovalbumin inhalation.

Animals—Thirteen 7- to 8-week-old calves.

Procedures—The efferent lymphatic duct of the caudal mediastinal lymph node of each calf was cannulated 3 or 4 days before experiment commencement. Calves were inoculated (day 0) with BRSV (n = 7) or BRSV-free tissue culture medium (mock exposure; 6) via aerosolization and exposed to aerosolized ovalbumin on days 1 through 6 and day 15. An efferent lymph sample was collected daily from each calf on days −1 through 16; CD4+ and CD8+ T lymphocyte subsets in lymph samples were enumerated with a fluorescence-activated cell scanner. Expressions of several cytokines by efferent lymphocytes and lymph ovalbumin-specific IgE concentration were measured. Each calf was euthanized on day 16 and then necropsied for evaluation of lungs.

Results—Mean fold increase in ovalbumin-specific IgE concentration was greater in BRSV-infected calves than in mock-infected calves. At various time points from days 4 through 10, percentages of T lymphocyte subsets and CD4+:CD8+ T lymphocyte ratios differed between BRSV-infected calves and day −1 values or from values in mock-infected calves. On days 3 through 5, IL-4 and IL-13 gene expressions in BRSV-infected calves were increased, compared with expressions in mock-infected calves. Lung lesions were consistent with antigen exposure.

Conclusions and Clinical Relevance—In response to the inhalation of aerosolized ovalbumin, BRSV infection in calves appeared to facilitate induction of a T helper 2 cell response and ovalbumin-specific IgE production.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare the effects of an orally administered corticosteroid (prednisone), an inhaled corticosteroid (flunisolide), a leukotriene-receptor antagonist (zafirlukast), an antiserotonergic drug (cyproheptadine), and a control substance on the asthmatic phenotype in cats with experimentally induced asthma.

Animals—6 cats with asthma experimentally induced by the use of Bermuda grass allergen (BGA).

Procedures—A randomized, crossover design was used to assess changes in the percentage of eosinophils in bronchoalveolar lavage fluid (BALF); airway hyperresponsiveness; blood lymphocyte phenotype determined by use of flow cytometry; and serum and BALF content of BGA-specific IgE, IgG, and IgA determined by use of ELISAs.

Results—Mean ± SE eosinophil percentages in BALF when cats were administered prednisone (5.0 ± 2.3%) and flunisolide (2.5 ± 1.7%) were significantly lower than for the control treatment (33.7 ± 11.1%). We did not detect significant differences in airway hyperresponsiveness or lymphocyte surface markers among treatments. Content of BGA-specific IgE in serum was significantly lower when cats were treated with prednisone (25.5 ± 5.4%), compared with values for the control treatment (63.6 ± 12.9%); no other significant differences were observed in content of BGA-specific immunoglobulins among treatments.

Conclusions and Clinical Relevance—Orally administered and inhaled corticosteroids decreased eosinophilic inflammation in airways of cats with experimentally induced asthma. Only oral administration of prednisone decreased the content of BGAspecific IgE in serum; no other significant local or systemic immunologic effects were detected among treatments. Inhaled corticosteroids can be considered as an alternate method for decreasing airway inflammation in cats with asthma. (Am J Vet Res 2005;66:1121–1127)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate changes in cysteinyl leukotriene (LT) concentrations in urine and bronchoalveolar lavage fluid (BALF) in cats with experimentally induced asthma.

Animals—19 cats with experimentally induced asthma and 5 control cats.

Procedure—Cats were sensitized to Bermuda grass or house dust mite allergen, and phenotypic features of asthma were confirmed with intradermal skin testing, evaluation of BALF eosinophil percentages, and pulmonary function testing. A competitive ELISA kit for LTC4, LTD4, and LTE4 was used for quantitative analysis of LTs. Urinary creatinine concentrations and BALF total protein (TP) concentrations were measured, and urinary LT-to-creatinine ratios and BALF LTto- TP ratios were calculated.

Results—Mean urinary LT-to-creatinine ratios did not differ significantly between control cats and allergensensitized cats before or after sensitization and challenge exposure with saline (0.9% NaCl) solution or allergen, respectively. In BALF, the mean LT-to-TP ratio of control cats did not differ significantly before or after sensitization and challenge exposure with saline. Asthmatic cats had BALF LT-to-TP ratios that were significantly lower than control cats at all time points, whereas ratios for asthmatic cats did not differ significantly among the various time points.

Conclusions and Clinical Relevance—Although LTs were readily detectable in urine, no significant increases in urinary LT concentrations were detected after challenge in allergen-sensitized cats. Spot testing of urinary LT concentrations appears to have no clinical benefit for use in monitoring the inflammatory asthmatic state in cats. The possibility that cysteinyl LTs bind effectively to their target receptors in BALF and, thus, decrease free LT concentrations deserves further study. (Am J Vet Res 2003;64:1449–1453)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To study the local immune response of calves to bovine respiratory syncytial virus (BRSV) infection with emphasis on IgE production and cytokine gene expression in pulmonary lymph.

Animals—Twelve 6- to 8-week-old Holstein bull calves. Six similar control calves were mock infected to obtain control data.

Procedure—Lymphatic cannulation surgery was performed on 12 calves to create a long-term thoracic lymph fistula draining to the exterior. Cannulated calves were exposed to virulent BRSV by aerosol. Lymph fluid collected daily was assayed for BRSV and isotype-specific IgE antibody, total IgG, IgA, IgM, and protein concentrations. Interleukin-4 (IL-4), interleukin- 2 (IL-2), and interferon-γ were semi-quantitated by reverse transcription-polymerase chain reaction (RT-PCR). Cell counts and fluorescence-activated cell scanner (FACSCAN) analysis of T-cell subsets were performed on lymph cells.

Results—Calves had clinical signs of respiratory tract disease during days 5 to 10 after infection and shed virus. Bovine respiratory syncytial virus-specific IgE in infected calves was significantly increased over baseline on day 9 after infection. Mean virus-specific IgE concentrations strongly correlated with increases in severity of clinical disease (r = 0.903). Expression of IL-2, IL-4, and interferon-γ was variably present in infected and control calves, with IL-4 expression most consistent during early infection.

Conclusions and Clinical Relevance—Infection with BRSV was associated with production of BRSV-specific IgE, and IL-4 message was commonly found in lymph cells of infected calves. This finding supports the concept that BRSV-induced pathophysiology involves a T helper cell type-2 response. Effective therapeutic and prophylactic strategies could, therefore, be developed using immunomodulation to shift the immune response more toward a T helper cell type-1 response. (Am J Vet Res 2000;61:291–298)

Full access
in American Journal of Veterinary Research