help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on August 11, 2004, doi:10.1164/rccm.200405-681OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 10, November 2004, 1043-1048

A more recent version of this article appeared on November 15, 2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200405-681OCv1
170/10/1043    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kumar, R. K
Right arrow Articles by Foster, P. S
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kumar, R. K
Right arrow Articles by Foster, P. S

Submitted on June 1, 2004
Accepted on August 6, 2004

Effects of Anti-Cytokine Therapy in a Mouse Model of Chronic Asthma

Rakesh K Kumar1*, Cristan Herbert1, Dianne C Webb2, Lily Li3, and Paul S Foster4

1 Department of Pathology, University of New South Wales, Sydney, NSW, Australia, 2 Division of Molecular Biosciences, Australian National University, John Curtin School of Medical Research, Canberra, ACT, Australia, 3 Immunobiology Research, Centocor Inc., Malvern, PA, USA, 4 Division of Molecular Biosciences, Australian National University, John Curtin School of Medical Research, Canberra, ACT, Australia; Discipline of Immunology and Microbiology, University of Newcastle, Faculty of Health, Newcastle, NSW, Australia

* To whom correspondence should be addressed. E-mail: r.kumar{at}unsw.edu.au.

The relative contribution of Th2 and Th1 cytokines to the pathogenesis of lesions of chronic asthma remains poorly understood. To date, therapeutic inhibition of Th2 cytokines has proved disappointing. We used a clinically relevant model of chronic allergic asthma in mice, to compare the effects of administering neutralizing antibodies to interleukin-13, interleukin-5 and interferon-{gamma} to animals with established disease. As has been observed in clinical studies, anti-interleukin-5 inhibited both inflammation and remodeling, but had no effect on airway responsiveness to methacholine. Anti-interleukin-13 effectively suppressed eosinophil recruitment and accumulation of chronic inflammatory cells in the airways. This treatment also partially suppressed changes of airway wall remodeling, including goblet cell hyperplasia/metaplasia and subepithelial fibrosis, but had limited ability to inhibit airway hyper-reactivity. In contrast, treatment with anti-interferon-{gamma} markedly suppressed airway hyper-reactivity. This antibody inhibited accumulation of chronic inflammatory cells but did not affect eosinophil recruitment or changes of remodeling. We conclude that inhibition of interleukin-5 is beneficial and inhibition of interleukin-13 has considerable potential as a therapeutic strategy in chronic asthma; that interferon-{gamma} may play an important role in the pathogenesis of airway hyper-reactivity; and that co-operative interaction between Th2 and Th1 cytokines contributes to the pathogenesis of the lesions of chronic asthma.
Key words: interleukin-5, interleukin-13, interferon-{gamma}, bronchial hyperreactivity, airway remodeling




This article has been cited by other articles:


Home page
 J. Immunol.Home page
D. C. Newcomb, W. Zhou, M. L. Moore, K. Goleniewska, G. K. K. Hershey, J. K. Kolls, and R. S. Peebles Jr.
A Functional IL-13 Receptor Is Expressed on Polarized Murine CD4+ Th17 Cells and IL-13 Signaling Attenuates Th17 Cytokine Production
J. Immunol., May 1, 2009; 182(9): 5317 - 5321.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Cai, R. K. Kumar, J. Zhou, P. S. Foster, and D. C. Webb
Ym1/2 Promotes Th2 Cytokine Expression by Inhibiting 12/15(S)-Lipoxygenase: Identification of a Novel Pathway for Regulating Allergic Inflammation
J. Immunol., May 1, 2009; 182(9): 5393 - 5399.
[Abstract] [Full Text] [PDF]

Home page
 DMMHome page
A. T. Nials and S. Uddin
Mouse models of allergic asthma: acute and chronic allergen challenge
Dis. Model. Mech., November 1, 2008; 1(4-5): 213 - 220.
[Abstract] [Full Text] [PDF]

Home page
 International Journal of ToxicologyHome page
P. L. Martin, D. Fisher, W. Glass, K. O'Neil, A. Das, E. C. Martin, and L. Li
Preclinical Safety and Pharmacology of an Anti-Human Interleukin-13 Monoclonal Antibody in Normal Macaques and in Macaques with Allergic Asthma
International Journal of Toxicology, September 1, 2008; 27(5): 351 - 358.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
M. D. Smithgall, M. R. Comeau, B.-R. Park Yoon, D. Kaufman, R. Armitage, and D. E. Smith
IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK Cells
Int. Immunol., August 1, 2008; 20(8): 1019 - 1030.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
E. R. Walsh, N. Sahu, J. Kearley, E. Benjamin, B. H. Kang, A. Humbles, and A. August
Strain-specific requirement for eosinophils in the recruitment of T cells to the lung during the development of allergic asthma
J. Exp. Med., June 9, 2008; 205(6): 1285 - 1292.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y.-C. Su, M. S. Rolph, N. G. Hansbro, C. R. Mackay, and W. A. Sewell
Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation
J. Immunol., February 15, 2008; 180(4): 2600 - 2607.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
O. Tliba and Y. Amrani
Airway Smooth Muscle Cell as an Inflammatory Cell: Lessons Learned from Interferon Signaling Pathways
Proceedings of the ATS, January 1, 2008; 5(1): 106 - 112.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. Pilling, D. Roife, M. Wang, S. D. Ronkainen, J. R. Crawford, E. L. Travis, and R. H. Gomer
Reduction of Bleomycin-Induced Pulmonary Fibrosis by Serum Amyloid P
J. Immunol., September 15, 2007; 179(6): 4035 - 4044.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J. C. Horvat, K. W. Beagley, M. A. Wade, J. A. Preston, N. G. Hansbro, D. K. Hickey, G. E. Kaiko, P. G. Gibson, P. S. Foster, and P. M. Hansbro
Neonatal Chlamydial Infection Induces Mixed T-Cell Responses That Drive Allergic Airway Disease
Am. J. Respir. Crit. Care Med., September 15, 2007; 176(6): 556 - 564.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
C. M. Lloyd and D. S. Robinson
Allergen-induced airway remodelling
Eur. Respir. J., May 1, 2007; 29(5): 1020 - 1032.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. G. Karras, J. R. Crosby, M. Guha, D. Tung, D. A. Miller, W. A. Gaarde, R. S. Geary, B. P. Monia, and S. A. Gregory
Anti-Inflammatory Activity of Inhaled IL-4 Receptor-{alpha} Antisense Oligonucleotide in Mice
Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 276 - 285.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
P. C. Fulkerson, C. A. Fischetti, and M. E. Rothenberg
Eosinophils and CCR3 Regulate Interleukin-13 Transgene-Induced Pulmonary Remodeling
Am. J. Pathol., December 1, 2006; 169(6): 2117 - 2126.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J. L. S. Lofgren, M. R. Mazan, E. P. Ingenito, K. Lascola, M. Seavey, A. Walsh, and A. M. Hoffman
Restrained whole body plethysmography for measure of strain-specific and allergen-induced airway responsiveness in conscious mice
J Appl Physiol, November 1, 2006; 101(5): 1495 - 1505.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. S. Siegle, N. Hansbro, C. Herbert, M. Yang, P. S. Foster, and R. K. Kumar
Airway Hyperreactivity in Exacerbation of Chronic Asthma Is Independent of Eosinophilic Inflammation
Am. J. Respir. Cell Mol. Biol., November 1, 2006; 35(5): 565 - 570.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
I. Meyts, P. W. Hellings, G. Hens, B. M. Vanaudenaerde, B. Verbinnen, H. Heremans, P. Matthys, D. M. Bullens, L. Overbergh, C. Mathieu, et al.
IL-12 Contributes to Allergen-Induced Airway Inflammation in Experimental Asthma
J. Immunol., November 1, 2006; 177(9): 6460 - 6470.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
T. Koya, K. Takeda, T. Kodama, N. Miyahara, S. Matsubara, A. Balhorn, A. Joetham, A. Dakhama, and E. W. Gelfand
RANTES (CCL5) Regulates Airway Responsiveness after Repeated Allergen Challenge
Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 147 - 154.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. Koch, M. Witzenrath, C. Reuter, M. Herma, H. Schutte, N. Suttorp, H. Collins, and S. H. E. Kaufmann
Role of Local Pulmonary IFN-{gamma} Expression in Murine Allergic Airway Inflammation
Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 211 - 219.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. Careau, L.-I. Proulx, P. Pouliot, A. Spahr, V. Turmel, and E. Y. Bissonnette
Antigen sensitization modulates alveolar macrophage functions in an asthma model
Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L871 - L879.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
S. N. Georas, J. Guo, U. De Fanis, and V. Casolaro
T-helper cell type-2 regulation in allergic disease
Eur. Respir. J., December 1, 2005; 26(6): 1119 - 1137.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Ozaki, Y.-i. Seki, A. Fukushima, and M. Kubo
The Control of Allergic Conjunctivitis by Suppressor of Cytokine Signaling (SOCS)3 and SOCS5 in a Murine Model
J. Immunol., October 15, 2005; 175(8): 5489 - 5497.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
H. Weigt, C. Nassenstein, T. Tschernig, P. F. Muhlradt, N. Krug, and A. Braun
Efficacy of Macrophage-activating Lipopeptide-2 Combined with Interferon-{gamma} in a Murine Asthma Model
Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 566 - 572.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. D. Sly, D. J. Turner, R. A. Collins, and Z. Hantos
Penh Is Not a Validated Technique for Measuring Airway Function in Mice
Am. J. Respir. Crit. Care Med., July 15, 2005; 172(2): 256 - 256.
[Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Schwartzbaum, A. Ahlbom, B. Malmer, S. Lonn, A. J. Brookes, H. Doss, W. Debinski, R. Henriksson, and M. Feychting
Polymorphisms Associated with Asthma Are Inversely Related to Glioblastoma Multiforme
Cancer Res., July 15, 2005; 65(14): 6459 - 6465.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. Mimura, Y. Shinozaki, H. Kawasaki, and H. Iwamura
JTP-27536 [(+)-1,3-Dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-Cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate Monohydrate], a Novel Inhibitor of Immunoglobulins and Interleukin-5 with Anti-Inflammatory Properties in Mouse Allergic Dermatitis Model
J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 293 - 301.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
L. Fabbri, S. P. Peters, I. Pavord, S. E. Wenzel, S. C. Lazarus, W. MacNee, F. Lemaire, and E. Abraham
Allergic Rhinitis, Asthma, Airway Biology, and Chronic Obstructive Pulmonary Disease in AJRCCM in 2004
Am. J. Respir. Crit. Care Med., April 1, 2005; 171(7): 686 - 698.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2004 American Thoracic Society