Effect of lack of Interleukin-4, Interleukin-12, Interleukin-18, or the Interferon-gamma receptor on virus replication, cytokine response, and lung pathology during respiratory syncytial virus infection in mice.

RSV is an important cause of bronchiolitis in infants. Immunopathology may play a role in RSV-induced bronchiolitis and severe RSV-induced disease has been associated with a Th2 type immune response. The aim of the study was to identify cytokine pathways that are crucial in influencing RSV-induced disease. For that purpose we inoculated IFNgammaR-/-, IL-12-/-, IL-18-/-, or IL-4-/- mice with RSV. We observed that an RSV infection resulted in a predominant Th1 cytokine response associated with slight bronchiolitis and alveolitis. Pulmonary histopathology was only aggravated in IFN R-/- mice, characterised by eosinophilic influx around the bronchioles. Despite subtle changes in cytokine expression, no differences in histopathology were observed in IL-12-/- and IL-18-/- mice. Deficiency of IL-4 has no effect on RSV-induced Th1 cytokines and pulmonary histopathology. IFNgamma-receptor deficiency during primary RSV infection resulted in a disturbed Th1 response based on increased IL-4, IL-5, and IL-13 expression and the presence of eosinophils in the lungs. It is concluded that IFNgamma signalling is required for a pronounced Th1 response to RSV while IL-12 and IL-18 are not. A shift in the balance between Th1 and Th2 towards a Th2 response induced by missing IFNgamma signalling leads to aggravated pulmonary pathology. This is not caused by enhanced viral load.