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Bronchobini® Ingredients (BRO) Prevent Rhinovirus Infection in Viable Mouse Lung Tissue
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A5483 - Bronchobini® Ingredients (BRO) Prevent Rhinovirus Infection in Viable Mouse Lung Tissue
Author Block: K. Sewald1, N. Hirth2, J. Warnecke2, O. Danov1, H. Obernolte1, A. Braun1, S. Wronski1; 1Fraunhofer ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Centre for Lung Research (DZL), Hannover, Germany, 2Biologische Heilmittel Heel GmbH, Baden-Baden, Germany.
Human rhinovirus (HRV) is a major cause of respiratory infections and a risk factor of exacerbations in patients with severe chronic pulmonary diseases. The virus invades into host airway epithelial cells, replicates and assembles new virions without inducing a strong cytopathic effect. The innate immune response against the virus activates diverse signalling pathways, leading to secretion of pro-inflammatory cytokines in order to mediate the anti-viral host response. The aim of the study was to test the efficacy of Bronchobini’s ingredients (BRO) in rhinovirus infection of fresh lung tissue.
Murine precision-cut lung slices (PCLS) containing airways were prepared from fresh lung tissue. Slices were inoculated with HRV1b, UV-inactivated HRV, medium or HRV in presence of BRO for 24h at 33°C. After cultivation, viral load was determined by TCID50 assay and tissue viability was evaluated. Cytokine profiles were determined by ELISA.
HRV induced release of cytokines IFN-γ induced protein 10 (IP-10) and Monocyte Chemoattractant Protein-1 (MCP-1) in viable lung tissue ex vivo. IP-10 is a key mediator of antiviral host response and a serum biomarker for acute respiratory infections, correlating with disease severity. It is produced in response to IFN-γ by a variety of cells, including monocytes, endothelial cells, epithelial cells and has been attributed several functions including chemoattraction for monocytes/macrophages, NK cells and T cells. Similarly, MCP-1 is a chemokine secreted upon infection and involved in recruitment of inflammatory cells. Therefore, both chemokines were used as early biomarker for recruitment of inflammatory cells in later phases of the infection. BRO showed a strong dose dependent efficacy effect on the HRV induced cytokines IFN-γ induced protein 10 (IP-10) and Monocyte Chemoattractant Protein-1 (MCP-1). While IP-10 was reduced to baseline levels by BRO, the levels of MCP-1 were even lower in the BRO high dose compared to the baseline, indicating a suppression of the baseline MCP-1. Infection of murine PCLS with HRV1b confirmed viral load by TCID50 assay which was not significantly changed by treatment with BRO. However, epithelial cells as target cells for HRV infection are only a small population in PCLS. Therefore, the amount of actually infected cells and release of new virions upon replication cannot be detected by TCID50 assay.
In summary, HRV1b infection of ex vivo lung tissue induced anti-viral and pro-inflammatory immune responses. This HRV-induced immune response was reduced after intervention with BRO after 24h.
Author Block: K. Sewald1, N. Hirth2, J. Warnecke2, O. Danov1, H. Obernolte1, A. Braun1, S. Wronski1; 1Fraunhofer ITEM, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Centre for Lung Research (DZL), Hannover, Germany, 2Biologische Heilmittel Heel GmbH, Baden-Baden, Germany.
Human rhinovirus (HRV) is a major cause of respiratory infections and a risk factor of exacerbations in patients with severe chronic pulmonary diseases. The virus invades into host airway epithelial cells, replicates and assembles new virions without inducing a strong cytopathic effect. The innate immune response against the virus activates diverse signalling pathways, leading to secretion of pro-inflammatory cytokines in order to mediate the anti-viral host response. The aim of the study was to test the efficacy of Bronchobini’s ingredients (BRO) in rhinovirus infection of fresh lung tissue.
Murine precision-cut lung slices (PCLS) containing airways were prepared from fresh lung tissue. Slices were inoculated with HRV1b, UV-inactivated HRV, medium or HRV in presence of BRO for 24h at 33°C. After cultivation, viral load was determined by TCID50 assay and tissue viability was evaluated. Cytokine profiles were determined by ELISA.
HRV induced release of cytokines IFN-γ induced protein 10 (IP-10) and Monocyte Chemoattractant Protein-1 (MCP-1) in viable lung tissue ex vivo. IP-10 is a key mediator of antiviral host response and a serum biomarker for acute respiratory infections, correlating with disease severity. It is produced in response to IFN-γ by a variety of cells, including monocytes, endothelial cells, epithelial cells and has been attributed several functions including chemoattraction for monocytes/macrophages, NK cells and T cells. Similarly, MCP-1 is a chemokine secreted upon infection and involved in recruitment of inflammatory cells. Therefore, both chemokines were used as early biomarker for recruitment of inflammatory cells in later phases of the infection. BRO showed a strong dose dependent efficacy effect on the HRV induced cytokines IFN-γ induced protein 10 (IP-10) and Monocyte Chemoattractant Protein-1 (MCP-1). While IP-10 was reduced to baseline levels by BRO, the levels of MCP-1 were even lower in the BRO high dose compared to the baseline, indicating a suppression of the baseline MCP-1. Infection of murine PCLS with HRV1b confirmed viral load by TCID50 assay which was not significantly changed by treatment with BRO. However, epithelial cells as target cells for HRV infection are only a small population in PCLS. Therefore, the amount of actually infected cells and release of new virions upon replication cannot be detected by TCID50 assay.
In summary, HRV1b infection of ex vivo lung tissue induced anti-viral and pro-inflammatory immune responses. This HRV-induced immune response was reduced after intervention with BRO after 24h.
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