Mechanisms of rhinovirus-induced asthma

Abstract

Several epidemiological studies using sensitive detection methodologies have confirmed that the majority of acute asthma exacerbations follow upper respiratory tract infections--common colds. Most of these colds are due to human rhinoviruses (RVs). RVs are able to reach and replicate in epithelial cells of the lower airways and can activate these cells to produce pro-inflammatory mediators. Under some circumstances, RVs can also become cytotoxic to the epithelium. Atopic asthmatic individuals produce less interferon-gamma and more interleukin-10 than normal subjects in response to RV infection. Symptom severity as well as viral shedding after experimental RV infection, is inversely correlated with 'atopic' status, expressed as the interferon-gamma to interleukin-5 ratio. Expression of co-stimulatory molecules on immune cells is also affected in atopic asthmatics, suggesting an aberrant immune response to RV that may lead to suboptimal viral clearance and viral persistence. Some of the above effects can be reversed in vitro by corticosteroids, second-generation antihistamines or anti-oxidants; however, the optimal strategy for treating acute asthma exacerbations requires further research at both mechanistic and clinical levels.

The impact of respiratory viruses on lung health after preterm birth

“…Furthermore, despite strong epidemiological evidence supporting the role of RV in the pathogenesis of asthma, airway reactivity and airflow limitation, the underlying mechanisms are unclear. Although damage to the developing airways and altered immune responses are thought to be the main mechanisms through which RV could induce asthma and airway hyperreactivity later in life [107,108], others have suggested that early-life infection with RV might be the first indication of the pre-existing tendency in some children to develop asthma, including among preterm infants [109,110]. The ability of RV to induce prolonged and exaggerated inflammatory responses after the initial infection has been described as a potential contributor to the development of chronic respiratory morbidity among preterm infants, with limited data demonstrating increased airway secretion of inflammatory cytokines and remodelling molecules during acute RV infection, particularly among those with BPD [108,111].…”

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

“…This observation was associated with increased paracellular permeability, effects that appear to be related to viral replication in immortalised cell lines grown as polarised monolayers [133], but may be amplified by pro-inflammatory cytokines [134]. In experimental and naturally occurring HRV-induced infection, airway epithelial cell and inflammatory-immune effector cell activation has been described with cytokines, chemokines and growth factor production associated with increased release of histamine and eosinophil cationic protein [135][136][137][138][139]. Recruitment of neutrophils, eosinophils, mast cells and CD4 + and CD8 + T-cells has been demonstrated through increased release of IL-6, IL-8, IL-16, IFN-γ-induced protein-10, eotaxin, RANTES, leukotrienes and other pro-inflammatory cytokines [137,140,141].…”

Childhood asthma and infection: virus-induced exacerbations as determinants and modifiers: Figure 1–

“…RV infection activates inflammatory pathways by increasing levels of neutrophils, eosinophils, CD4+ cells, CD8+ cells and mast cells through increased mRNA expression and translation of IL-6, IL-8, IL-16, eotaxin, interferon (IFN)-c-inducible protein (IP) 10, CC chemokine ligand 5 (RANTES) and other pro-inflammatory cytokines and chemokines [66]. Moreover, viruses generate systemic as well as neural responses, further inducing inflammation and hyperresponsiveness.…”