Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma.
Atopic asthma is characterized by chronic inflammation of the bronchial mucosa in which eosinophil- and immunoglobulin E (IgE)-dependent mechanisms are believed to be prominent. Therefore, specific proeosinophilic mediators such as interleukin (IL)-5 and essential cofactors for IgE switching in B-lymphocytes such as IL-4 could play a pivotal role in asthma. However, the exact role that individual inflammatory mediators play in the development of the disease in humans is still unknown. Using semiquantitative reverse transcriptase-polymerase chain reaction amplification in bronchial biopsies from 10 atopic asthmatics, we have tested the hypothesis that IL-4 and IL-5 mRNA expression relative to beta-actin mRNA correlates with validated indicators of disease severity. IL-4 and IL-5 mRNA copies relative to beta-actin mRNA were detected in bronchial biopsies from atopic asthmatics. The numbers of IL-5 mRNA copies relative to beta-actin mRNA correlated with disease severity assessed by the Aas asthma score (r = 0.70, p = 0.01), baseline FEV1 (r = -0.94, p = 0.001), baseline peak expiratory flow rate (r = -0.77, p = 0.01), peak expiratory flow rate variability over 2 wk (r = 0.69, p = 0.028), and the histamine PC20 (r = -0.72, p = 0.018). Conversely, the numbers of IL-4 mRNA copies relative to beta-actin mRNA did not correlate with asthma severity, but they positively correlated with total serum IgE concentrations (r = -0.90, p = 0.001). Our present results support the concept that IL-5 may determine asthma clinical expression and severity, and by inference they support the development of IL-5 targeted therapies.
Humbert
M
M
Allergy and Clinical Immunology, Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom.
Corrigan
C J
CJ
Kimmitt
P
P
Till
S J
SJ
Kay
A B
AB
Durham
S R
SR
D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001706:Biopsy; D001980:Bronchi / Q000737:chemistry*; D016022:Case-Control Studies; D005541:Forced Expiratory Volume; D015870:Gene Expression / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications*; D007073:Immunoglobulin E / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis*; D015848:Interleukin-5 / Q000032:analysis*; D009092:Mucous Membrane; D010366:Peak Expiratory Flow Rate; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D015203:Reproducibility of Results; D012720:Severity of Illness Index
D015848:Interleukin-5; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E