Effect of infection with bovine respiratory syncytial virus on pulmonary clearance of an inhaled antigen in calves

Laurel J. Gershwin Department of Pathology, Microbiology, & Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Robert A. Gunther Department of Surgery, School of Medicine, University of California, Davis, CA 95616.

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William J. Hornof Department of Surgery & Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.

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Richard F. Larson Department of Surgery & Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA 95616.

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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.

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.

Contributor Notes

Supported by USDA National Research Initiative Grant No. USDA NRI 98-35204-6379.

Presented in part at the 81st Conference of Research Workers in Animal Diseases, Chicago, November 2000.

The authors thank Linda Talken for surgical assistance and Kathleen E. Friebertshauser, Kerrie Vaughan, and H. David Pettigrew for technical assistance.

Address correspondence to Dr. Gershwin.
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