The effect of IL-12 treatment on vaccine-enhanced illness during infection with respiratory syncytial virus.
In humans and mice, sensitisation to respiratory syncytial virus (RSV) antigens can result in severe inflammatory lung disease during subsequent infection with the virus. Although specific antiviral T cells are thought to be responsible for this augmentation of disease, the precise role of different functional subsets is unknown. BALB/c mice sensitised to the major surface glycoprotein (G) of RSV expressed by recombinant vaccinia virus develop Th2-driven lung eosinophilia after intranasal challenge with the virus. Mice treated with IL-12 at various times during vaccination and challenge, had reduced vaccine-induced lung eosinophilia but increased total pulmonary lymphoid cell infiltration. Intracellular cytokine analysis showed that interferon-gamma production during challenge was increased and IL-4 and IL-5 reduced by IL-12 treatment. Though IL-12 treatment reduced lung eosinophilia, illness (as assessed by weight loss) was not eliminated and sometimes increased. Reversing Th2-associated pathology with IL-12 does not necessarily benefit the host.
Openshaw
P J
PJ
Imperial College, St Mary's Hospital, London, U.K.
Hussell
T
T
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001990:Bronchiolitis, Viral / Q000150:complications / Q000276:immunology* / Q000517:prevention & control; D002648:Child; D004195:Disease Models, Animal; D015707:HN Protein; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology; D018664:Interleukin-12 / Q000627:therapeutic use*; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000276:immunology* / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000009:adverse effects* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015707:HN Protein; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G; D018664:Interleukin-12