Interleukin-5 and eosinophils as therapeutic targets for asthma.
Extensive clinical investigations have implicated eosinophils in the pathogenesis of asthma. In a recent clinical trial, humanized monoclonal antibody to interleukin (IL)-5 significantly limited eosinophil migration to the lung. However, treatment did not affect the development of the late-phase response or airways hyperresponsiveness in experimental asthma. Although IL-5 is a key regulator of eosinophilia and attenuation of its actions without signs of clinical improvement raises questions about the contribution of these cells to disease, further studies are warranted to define the effects of anti-IL-5 in the processes that lead to chronic asthma. Furthermore, eosinophil accumulation into allergic tissues should not be viewed as a process that is exclusively regulated by IL-5 but one in which IL-5 greatly contributes. Indeed, data on anti-IL-5 treatments (human and animal models) are confounded by the failure of this approach to completely resolve tissue eosinophilia and the belief that IL-5 alone is the critical molecular switch for eosinophil development and migration. The contribution of these IL-5-independent pathways should be considered when assessing the role of eosinophils in disease processes.
Foster
Paul S
PS
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT, 0200, Australia. Paul.Foster@anu.edu.au
Hogan
Simon P
SP
Yang
Ming
M
Mattes
Joerg
J
Young
Ian G
IG
Matthaei
Klaus I
KI
Kumar
Rakesh K
RK
Mahalingam
Surendran
S
Webb
Dianne C
DC
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D016535:Bronchial Hyperreactivity; D004195:Disease Models, Animal; D004802:Eosinophilia; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D008954:Models, Biological
D015848:Interleukin-5