Journal Article

Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production

Contoli, Marco, Johnston, Sebastian L, Stanciu, Luminita A, Kebadze, Tatiana, Jeffery, Peter K, Papi, Alberto, Laza-Stanca, Vasile, Message, Simon D, Kon, Onn M, Mallia, Patrick, Sanderson, Gwen, Parker, Hayley L, Zhu, Jie

2008

Overview

Acute exacerbations are the major cause of asthma morbidity, mortality, and health-care costs and are difficult to treat and prevent. The majority of asthma exacerbations are associated with rhinovirus (RV) infection, but evidence supporting a causal relationship is weak and mechanisms are poorly understood. We hypothesized that in asthmatic, but not normal, subjects RV infection would induce clinical, physiologic, and pathologic lower airway responses typical of an asthma exacerbation and that these changes would be related to virus replication and impaired T helper 1 (Th1)/IL-10 or augmented Th2 immune responses. We investigated physiologic, virologic, and immunopathologic responses to experimental RV infection in blood, induced sputum, and bronchial lavage in 10 asthmatic and 15 normal volunteers. RV infection induced significantly greater lower respiratory symptoms and lung function impairment and increases in bronchial hyperreactivity and eosinophilic lower airway inflammation in asthmatic compared with normal subjects. In asthmatic, but not normal, subjects virus load was significantly related to lower respiratory symptoms, bronchial hyperreactivity, and reductions in blood total and CD8⁺ lymphocytes; lung function impairment was significantly related to neutrophilic and eosinophilic lower airway inflammation. The same virologic and clinical outcomes were strongly related to deficient IFN-γ and IL-10 responses and to augmented IL-4, IL-5, and IL-13 responses. This study demonstrates increased RV-induced clinical illness severity in asthmatic compared with normal subjects, provides evidence of strong relationships between virus load, lower airway virus-induced inflammation and asthma exacerbation severity, and indicates augmented Th2 or impaired Th1 or IL-10 immunity are likely important mechanisms.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Asthma / Asthma - immunology / Asthma - metabolism / Biological Sciences / Blood / Bronchoalveolar Lavage / CD4-positive T-lymphocytes / Cells, Cultured / Correlation analysis / Cytokines / Cytokines - biosynthesis / Cytokines - immunology / Diseases / Health / health care costs / Humans / Hypersensitivity / immune response / Infections / Inflammation / interferon-gamma / interleukin-10 / interleukin-13 / interleukin-4 / interleukin-5 / Leukocytes - cytology / Leukocytes - immunology / lung function / Lungs / Lymphocytes / morbidity / mortality / Peak expiratory flow rate / Picornaviridae Infections - immunology / Picornaviridae Infections - metabolism / Picornaviridae Infections - pathology / Picornaviridae Infections - physiopathology / Respiratory function / Rhinovirus / Rhinovirus - immunology / Studies / T lymphocytes / Th1 Cells - immunology / Th1 Cells - metabolism / Th2 Cells - immunology / Th2 Cells - metabolism / Tissue Culture Techniques / viral load / virus replication / Viruses / volunteers