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  • Author or Editor: Laurel J. Gershwin x
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SUMMARY

Immunoglobulin E is produced in response to parasitic nematodes that undergo blood and tissue migrations. Results of our previous studies indicated that IgE and IgG respond to Dirofilaria immitis in experimentally infected dogs. To determine the association between treatment with the larvicide, diethyl-carbamazine (dec), and antibody responses and to examine the potential influence of infection with a nonfilarid intestinal nematode on isotype-specific immune responses, we monitored, by use of isotype-specific elisa, separate IgE and IgG responses against D immitis in 4 groups (A-D) of 8 dogs experimentally coinfected with D immitis and Ancylostoma caninum. All dogs were monitored from 2 weeks before inoculation with D immitis, through postinoculation (pi) week 20. Group-B dogs received a daily regimen of 6.6 mg of dec/kg of body weight. Group-C dogs received 4.95 mg of oxibendazole/kg daily. Group-D dogs received dec and oxibendazole, equivalent to the daily doses given to dogs of groups B and C. All dogs given oxibendazole had no A caninum at necropsy. Of the groups receiving dec, 3 group-B dogs each had 1 to 2 D immitis at necropsy. When results of chronologic IgE determination for all groups were statistically compared, only groups B and C had significant (P = 0.0148 and P ≪0.00005, respectively) increases in IgE values. Group-C dogs had the highest IgE values from pi week 10 until the end of the study, whereas IgG values were statistically identical to those of group-A dogs. Group-B dogs given only dec and having the least number of D immitis of all groups, had IgE values that peaked at pi week 6; values were significantly (P = 0.0002) higher than those for all other groups. In Group-B dogs, IgG values increased significantly (P ≪ 0.00005) only at pi week 20 and were significantly (P ≪ 0.00005) decreased after pi week 6, compared with values for all other groups. Group D containing 6 dogs infected with 1 to 18 D immitis found at necropsy had IgE values between those of group-B dogs and those of nondec-treated groups at pi week 6. There was no difference in IgG values between 3 groups at pi week 6, and IgE values were found to be a better correlator than were IgG values to the number of D immitis larvae killed in the tissues during this period. All differences in IgG and IgE values not only correlated with treatment status and number of D immitis adults found at necropsy, but also with the developmental stage of D immitis commonly present in the groups at each time point and the number of adult D immitis found at necropsy.

Free access
in American Journal of Veterinary Research

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
in Journal of the American Veterinary Medical Association

Summary

Cannulation of the celiac trunk was surgically performed in 26 Holstein steers. The procedure was successful in 23 (88.5%) of the steers. Twenty-two of the steers were infected either naturally or experimentally with the abomasal nematode, Ostertagia ostertagi and/or other gastrointestinal parasites. The remaining 4 steers were not infected. Lymph obtained after surgery was used in various immunologic and biochemical assays. Daily lymph flow rate and total and differential wbc counts were determined after surgeiy in 4 of the infected and 3 of the noninfected steers. Steers were euthanatized for tissue specimen collection 7 days after surgery. At the time of euthanasia, lymph was still flowing from the cannula of 13 (56.5%) of the steers in which surgeiy was successful. This surgical procedure represents a valuable technique for studying at the local level, immunologic and physiologic responses of cattle to infection with O ostertagi.

Free access
in American Journal of Veterinary Research

Summary

Pepsinogen and protein concentrations were determined in blood samples, collected from the left gastroepiploic artery and vein, and in abomasal lymph from 15 steers naturally infected with Ostertagia ostertagi and 4 uninfected steers. In steers with type-1 ostertagiosis, the concentration gradient between the mucosal interstitium and the blood alone could account for higher than normal serum pepsinogen concentrations. High interstitial pepsinogen concentrations may have resulted from increased epithelial permeability or increased pepsinogen production and secretion. However, in steers with type-2 ostertagiosis, the concentration gradient could not entirely account for the high serum pepsinogen concentrations, suggesting that capillary permeability or surface area may have been altered. Lymphatic uptake contributed pepsinogen to the blood in all infected steers.

Free 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 develop a system for analysis of immune response variables in the lymph draining the lung and to establish baseline data for clinically normal calves.

Design

Surgery was performed on 6 calves to insert a cannula into the efferent lymphatic duct of the caudal mediastinal lymph node to create a long-term thoracic lymph fistula draining to the exterior. Lymph was collected daily, and on the fifth postoperative day, calves were exposed to an aerosol of cell culture medium (mock infection). For the next 10 days, lymph was collected for analysis and, on the tenth day, necropsy was performed.

Animals

Six 6- to 8-week-old Holstein bull calves.

Procedures

Daily lymph samples were evaluated for: flow rate; total and differential cell counts; and IgG, IgM, IgA, IgE, and protein concentrations. On days −4, −1, 1, 4, 7, and 10, cells were stained and quantitated by fluorescence-activated cell sorter analysis for T, B, CD4+, and CD8+ cells. Blood lymphocytes were evaluated on days -1 and 10 for comparison.

Results

Flow was established for up to 25 days, with a mean rate between 11 and 22 ml/h. Protein concentrations in lymph and plasma did not indicate a protein drain. Although mean lymphocyte counts reflected a slight gradual decrease in lymph lymphocytes, this effect was not apparent in every calf, nor was the effect seen in blood lymphocytes. There were no significant changes in IgG, IgM, IgA, or IgE concentration, with the exception of IgA concentration in 1 calf that developed an abscess at the cannulation site. The T-cell subset absolute numbers of CD4+ and CD8+ cells decreased slightly over time, but the CD4+-to-CD8+ cell ratio remained almost constant at near 2.

Conclusions

Creation of a thoracic lymphatic fistula appears to be a useful technique for studying effects of lung infection on immunologic variables, with potential application to bacterial and viral respiratory tract diseases.

Clinical Relevance

Thoracic lymphatic cannulation can be used in studies to determine pathogenic mechanisms in respiratory tract disease and to develop more effective vaccines against respiratory tract pathogens.

Free 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

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