Viral Infections and Associated Factors That Promote Acute Exacerbations of Asthma

Kim, Chang-Keun; Callaway, Zak; Gern, James E.

Airway epithelial cells initially respond to RSV infection by releasing type I IFNs, IL-12, IL-18, 42 and a variety of cytokines and chemokines, including IL-8, IL-10, RANTES, macrophage inflammatory protein (MIP)-1α, monocyte chemotactic protein (MCP)-1, and eotaxin. 43 After migration to the lymph nodes for viral antigen presentation to T cells, dendritic cells migrate back to the infected epithelium, release mediators again (e.g., IFN-γ, IL-2, IL-4, IL-5, IL-9, and IL-12), and recruit additional inflammatory cells (e.g., CD8+ T cells and B cells), and granulocytes (neutrophils and Eos). 44 Under some circumstances, RSV infection may promote a T helper 2 (Th2) bias in immune responses in humans 41 and animals. 42 This was also found in a study comparing differential airway inflammatory responses in RSV-and influenza-induced asthma exacerbations. IFN-γ and TNF-α levels were significantly lower in RSV-induced asthma exacerbation when compared to asthmatics infected with influenza. 45 Indeed, the weaker Th1 response during viral infection in these individuals may lead to reduced viral clearance and prolonged and/or more serious disease. RSV infection is a potent inducer of chemokines, 46 and RANTES and eotaxin in particular have been associated with increased eosinophilia and RSV disease severity in mice. 47 Eotaxin appears to be a key component of Th2-driven disease, 48 and eotaxin levels correlate closely with eosinophil degranulation (i.e., eosinophil-derived neurotoxin [EDN] and ECP) in pediatric asthma. 49 Consequently, it may be a good therapeutic target in asthma and other eosinophil-related disease.