Journal Article

Virus-induced asthma attack: The importance of allergic inflammation in response to viral antigen in an animal model of asthma

Drake, Matthew G., Adamko, Darryl J., Skappak, Christopher, Wu, Ying-qi, Ilarraza, Ramses

2017

Overview

Asthma exacerbation can be a life-threatening condition, and is most often triggered by common respiratory viruses. Poor asthma control and worsening of respiratory function is associated with increased airway inflammation, including eosinophilia. Prevention of asthma exacerbation relies on treatment with corticosteroids, which preferentially inhibit allergic inflammation like eosinophils. Human studies demonstrate that inactivated virus can trigger eosinophil activation in vitro through antigen presentation and memory CD4+ lymphocytes. We hypothesized that animals with immunologic memory to a respiratory virus would also develop airway hyperresponsiveness in response to a UV-inactivated form of the virus if they have pre-existing allergic airway inflammation. Guinea pigs were ovalbumin-sensitized, infected with live parainfluenza virus (PIV), aerosol-challenged with ovalbumin, and then re-inoculated 60 days later with live or UV-inactivated PIV. Some animals were either treated with dexamethasone prior to the second viral exposure. Lymphocytes were isolated from parabronchial lymph nodes to confirm immunologic memory to the virus. Airway reactivity was measured and inflammation was assessed using bronchoalveolar lavage and lung histology. The induction of viral immunologic memory was confirmed in infected animals. Allergen sensitized and challenged animals developed airway hyperreactivity with eosinophilic airway inflammation when re-exposed to UV-inactivated PIV, while non-sensitized animals did not. Airway hyperreactivity in the sensitized animals was inhibited by pre-treatment with dexamethasone. We suggest that the response of allergic inflammation to virus antigen is a significant factor causing asthma exacerbation. We propose that this is one mechanism explaining how corticosteroids prevent virus-induced asthma attack.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Activation analysis / Aerosols / Allergens / Alveoli / Animal models / Animals / Anti-Inflammatory Agents - therapeutic use / Antigen presentation / Antigens / Asthma / Asthma - drug therapy / Asthma - immunology / Asthma - virology / Biology and Life Sciences / Bronchoalveolar lavage / Bronchus / Care and treatment / CD4 antigen / Cell activation / Complications and side effects / Corticoids / Corticosteroids / Critical care / Deactivation / Departments / Development and progression / Dexamethasone / Dexamethasone - therapeutic use / Disease Models, Animal / Eosinophilia / Eosinophils / Exposure / Female / Guinea Pigs / Histology / Humans / Hypersensitivity / Immune response / Immunologic Memory - drug effects / Immunological memory / Immunology / In vitro methods and tests / Infections / Inflammation / Inflammation - drug therapy / Inflammation - immunology / Inflammation - virology / Influenza / Injections / Leukocytes (eosinophilic) / Lungs / Lymph nodes / Lymphocytes / Lymphocytes - immunology / Lymphocytes - virology / Medical research / Medicine / Medicine and Health Sciences / Memory / Ovalbumin / Parainfluenza / Parainfluenza Virus 1, Human - immunology / Pediatrics / Physiology / Pretreatment / Research and Analysis Methods / Respiratory function / Respiratory Hypersensitivity - drug therapy / Respiratory Hypersensitivity - immunology / Respiratory Hypersensitivity - virology / Respiratory tract / Respiratory tract diseases / Respirovirus Infections - complications / Respirovirus Infections - drug therapy / Respirovirus Infections - immunology / Ultraviolet radiation / Viral infections / Virus diseases / Viruses