Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma

被引:182
作者
Humbert, M [1 ]
Corrigan, CJ [1 ]
Kimmitt, P [1 ]
Till, SJ [1 ]
Kay, AB [1 ]
Durham, SR [1 ]
机构
[1] NATL HEART & LUNG INST,UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,SCH MED,LONDON SW3 6LY,ENGLAND
基金
英国惠康基金;
关键词
D O I
10.1164/ajrccm.156.3.9610033
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
引用
收藏
页码:704 / 708
页数:5
相关论文
共 29 条
[1]  
AAS K, 1981, ALLERGY, V36, P1
[2]   Generation of a variant of human interleukin-4 by alternative splicing [J].
Alms, WJ ;
Atamas, SP ;
Yurovsky, VV ;
White, B .
MOLECULAR IMMUNOLOGY, 1996, 33 (4-5) :361-370
[3]  
Atamas SP, 1996, J IMMUNOL, V156, P435
[4]   EOSINOPHILIC INFLAMMATION IN ASTHMA [J].
BOUSQUET, J ;
CHANEZ, P ;
LACOSTE, JY ;
BARNEON, G ;
GHAVANIAN, N ;
ENANDER, I ;
VENGE, P ;
AHLSTEDT, S ;
SIMONYLAFONTAINE, J ;
GODARD, P ;
MICHEL, FB .
NEW ENGLAND JOURNAL OF MEDICINE, 1990, 323 (15) :1033-1039
[5]   ATTENUATION OF ALLERGIC AIRWAY INFLAMMATION IN IL-4 DEFICIENT MICE [J].
BRUSSELLE, GG ;
KIPS, JC ;
TAVERNIER, JH ;
VANDERHEYDEN, JG ;
CUVELIER, CA ;
PAUWELS, RA ;
BLUETHMANN, H .
CLINICAL AND EXPERIMENTAL ALLERGY, 1994, 24 (01) :73-80
[6]   ALLERGEN-INDUCED INCREASE IN BRONCHIAL RESPONSIVENESS TO HISTAMINE - RELATIONSHIP TO THE LATE ASTHMATIC RESPONSE AND CHANGE IN AIRWAY CALIBER [J].
CARTIER, A ;
THOMSON, NC ;
FRITH, PA ;
ROBERTS, R ;
HARGREAVE, FE .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1982, 70 (03) :170-177
[7]   T-CELLS AND EOSINOPHILS IN THE PATHOGENESIS OF ASTHMA [J].
CORRIGAN, CJ ;
KAY, AB .
IMMUNOLOGY TODAY, 1992, 13 (12) :501-507
[8]   Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity [J].
Corry, DB ;
Folkesson, HG ;
Warnock, ML ;
Erle, DJ ;
Matthay, MA ;
WienerKronish, JP ;
Locksley, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (01) :109-117
[9]  
DELPRETE G, 1988, J IMMUNOL, V140, P4193
[10]   EFFECT OF HOUSE DUST MITE AVOIDANCE MEASURES ON ADULT ATOPIC ASTHMA [J].
DORWARD, AJ ;
COLLOFF, MJ ;
MACKAY, NS ;
MCSHARRY, C ;
THOMSON, NC .
THORAX, 1988, 43 (02) :98-102