Integrated signals between IL-13, IL-4, and IL-5 regulate airways hyperreactivity

被引:267
作者
Webb, DC
McKenzie, ANJ
Koskinen, AML
Yang, M
Mattes, J
Foster, PS [1 ]
机构
[1] Australian Natl Univ, John Curtin Sch Med Res, Div Biochem & Mol Biol, Canberra, ACT 0200, Australia
[2] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
关键词
D O I
10.4049/jimmunol.165.1.108
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ln this investigation, we have examined the integrated relationship between IL-13, IL-4, and IL-5 for the development of airways hyperreactivity (AHR) in a model of asthma in BALB/c mite. Sensitization and aeroallergen challenge of both wild-type (WT) and IL-13 gene-targeted (IL-13(-/-)) mice induced allergic disease that was characterized by pulmonary eosinophilia and AHR to beta-methacholine. Although these responses in IL-13-/- mice were heightened compared with WT, they could be reduced to the level in nonallergic mice by the concomitant neutralization of IL-4. Mice in which both IL-4 and IL-13 were depleted displayed a marked reduction in tissue eosinophils, despite the development of a blood eosinophilia, Similar neutralization of IL-4 in WT mice only partially reduced AHR with no effect on tissue eosinophilia, In addition, neutralization of IL-5 in IL-13(-/-) mice, but not in WT mice, inhibited AHR, suggesting that tissue eosinophilia is linked to the mechanism underlying AHR only in the absence of IL-13, Additionally, mucus hypersecretion was attenuated in IL-13(-/-) mice, despite the persistence of AHR. Taken together, our data suggest both a modulatory role for IL-13 during sensitization and a proinflammatory role during aeroallergen challenge. The latter process appears redundant with respect to IL-4.
引用
收藏
页码:108 / 113
页数:6
相关论文
共 49 条
[1]   Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice [J].
Akimoto, T ;
Numata, F ;
Tamura, M ;
Takata, Y ;
Higashida, N ;
Takashi, T ;
Takeda, K ;
Akira, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (09) :1537-1542
[2]  
BOCHNER BS, 1994, ANNU REV IMMUNOL, V12, P295
[3]   EVIDENCE OF ONGOING MAST-CELL AND EOSINOPHIL DEGRANULATION IN SYMPTOMATIC ASTHMA AIRWAY [J].
BROIDE, DH ;
GLEICH, GJ ;
CUOMO, AJ ;
COBURN, DA ;
FEDERMAN, EC ;
SCHWARTZ, LB ;
WASSERMAN, SI .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1991, 88 (04) :637-648
[4]   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
[5]  
Cohn L, 1998, J IMMUNOL, V161, P3813
[6]  
Cohn L, 1999, J IMMUNOL, V162, P6178
[7]   Induction of airway mucus production by T helper 2 (Th2) cells: A critical role for interleukin 4 in cell recruitment but not mucus production [J].
Cohn, L ;
Homer, RJ ;
Marinov, A ;
Rankin, J ;
Bottomly, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (10) :1737-1747
[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]  
Dabbagh K, 1999, J IMMUNOL, V162, P6233
[10]   The role of IL-13 and its receptor in allergy and inflammatory responses [J].
de Vries, JE .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1998, 102 (02) :165-169