The effects of prior immune manipulation on respiratory syncytial virus-induced pathogenesis.

摘要

Respiratory syncytial virus (RSV) causes illness ranging from mild coryza to severe bronchiolitis in infants during its annual epidemics. Disease severity appears to depend on variability in host rather than viral factors. Severe RSV disease correlates with type 2 immune responses. In order to determine whether predisposition to type 2 cytokine production can enhance subsequent RSV disease, experiments were performed in three mouse models characterized by elevated interleukin-4 (IL-4) production. Constitutive expression of IL-4 delays viral clearance and increases pathology. However, priming with schistosome eggs, which increases IL-4 in the lung, did not alter RSV disease. Pertussis toxin priming enhances RSV disease through non-IL-4-dependent mechanisms. These results indicate that the cytokine environment established prior to viral challenge can alter the immune response to RSV, and thereby alter disease expression. Immunomodulating agents affect RSV disease outcome in a treatment-specific manner, mediated through multiple effector pathways.