A short term mouse model that reproduces the immunopathological features of rhinovirus induced exacerbation of COPD

Viral exacerbations of chronic obstructive pulmonary disease (COPD), commonly caused by rhinovirus (RV) infection, are poorly controlled by current therapies. This is due to a lack of understanding of the underlying immunopathological mechanisms. Human studies have identified a number of key immune responses that are associated with RV-induced exacerbations including neutrophilic inflammation, expression of inflammatory cytokines and deficiencies in innate anti-viral interferon. Animal models of COPD exacerbation are required to determine the contribution of these responses to disease pathogenesis. We aimed to develop a short-term mouse model that reproduced the hallmark features of RV-induced exacerbation of COPD. Evaluation of complex protocols involving multiple dose elastase and lipopolysaccharide administration combined with RV1B infection showed suppression rather than enhancement of inflammatory parameters compared to control mice infected with RV1B alone. Therefore, these approaches did not accurately model the enhanced inflammation associated with RV infection in patients with COPD compared to healthy subjects. In contrast, a single elastase treatment followed by RV infection led to heightened airway neutrophilic and lymphocytic inflammation, increased expression of TNF-α, CXCL10/IP-10 and CCL5/RANTES, mucus hyper-secretion and preliminary evidence for increased airway hyper-responsiveness compared to mice treated with elastase or RV infection alone. In summar...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research