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

✍ Scribed by Anita Boelen; Joan Kwakkel; Marion Barends; Lia de Rond; Jan Dormans; Dr. Tjeerd Kimman

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 204 KB
• Volume: 66
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.2180

✦ Synopsis

Abstract

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 IFNγR^−/−^, 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. IFNγ‐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 IFNγ 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 IFNγ signalling leads to aggravated pulmonary pathology. This is not caused by enhanced viral load. J. Med. Virol. 66:552–560, 2002. © 2002 Wiley‐Liss, Inc.