Abstract BACKGROUND: Respiratory syncytial virus (RSV) is the major cause of severe lower respiratory tract infection in infants and young children. Recently RSV has also been recognized as a serious health risk in the elderly, but the pathogenesis of RSV infection in the elderly remains unknown. METHODS: Dynamics of pulmonary cytokine response (including IFN-gamma, IL-4, IL-10, IL-6, MCP-1, and GRO mRNA) during acute RSV infection were investigated in young (<2 months old) and aged (>9 months old) cotton rats S.hispidus. Therapeutic treatments that diminish viral replication (antiviral antibody) and pulmonary pathology (anti-inflammatory corticosteroid) in RSV-infected animals were used to evaluate contribution of virus replication and inflammation to the development of RSV disease with respect to age. RESULTS: The time of the peak expression of majority of cytokines was shifted with respect to age. Antiviral and anti-inflammatory treatments had similar effect on cytokine expression in aged and young animals. GRO mRNA transcripts were more abundant in the lungs of aged animals. CONCLUSIONS: The present work reports the age-related delay in the pulmonary cytokine response to RSV, imbalance in chemokine production with respect to age and underscores different components of RSV pathogenesis with respect to their molecular signature.