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