Role of CCL11 in eosinophilic lung disease during respiratory syncytial virus infection.
Respiratory syncytial virus (RSV) is a major viral pathogen of infants and the elderly. Significant morbidity is caused by an overexuberant mixed lung cell infiltrate, which is thought to be driven by chemokines. One of the main chemotactic mediators responsible for the movement of eosinophils is CCL11 (eotaxin). Using a mouse model of eosinophilic bronchiolitis induced by RSV, we show here that treatment in vivo with a blocking antibody to CCL11 greatly reduces lung eosinophilia and disease severity. In addition, anti-CCL11 caused a striking inhibition of CD4-T-cell influx and shifted cytokine production away from interleukin-5 without reducing the resistance to viral replication. These results suggest that in addition to influencing eosinophil diapedesis and survival, anti-CCL11 has an action on T cells. These studies strengthen the case for anti-CCL11 treatment of Th2-driven diseases.
Matthews
Stephen P
SP
Department of Respiratory Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London W2 1PG, UK.
Tregoning
John S
JS
Coyle
Anthony J
AJ
Hussell
Tracy
T
Openshaw
Peter J M
PJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000502:physiology*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology*
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC