|
|
||||||||||||||
|
|
|||||||||||||||
Leader |
Ludwig Institute for Cancer Research and Experimental Medicine Unit, Université Catholique de Louvain, B-1200 Brussels, Belgium
Dr Renauld Jean-Christophe.Renauld{at}bru.licr.org
Asthma is a triad of intermittent airway obstruction, bronchial smooth muscle cell hyperreactivity to bronchoconstrictors, and chronic bronchial inflammation. From an aetiological standpoint, asthma is a heterogenous disease, but often appears as a form of immediate hypersensitivity. Many patients with asthma have other manifestations of atopy, such as rhinitis or eczema. Even among non-atopic patients with asthma, the pathophysiology of airway constriction is similar, raising the hypothesis that alternative mechanisms of mast cell degranulation may underlie the disease. The primary inflammatory lesion of asthma consists of accumulation of CD4+ T helper type 2 (TH2) lymphocytes and eosinophils in the airway mucosa. TH2 cells orchestrate the asthmatic inflammation through the secretion of a series of cytokines, particularly interleukin 4 (IL-4), IL-13, IL-5, and IL-9. IL-4 is the major factor regulating IgE production by B cells, and is required for optimal TH2 differentiation. However, blocking IL-4 is not sufficient to inhibit the development of asthma in experimental models. In contrast, inhibition of IL-13, another TH2 cytokine whose signal transduction pathway overlaps with that of IL-4, completely blocks airway hyperreactivity in mouse asthma models. IL-5 is a key factor for eosinophilia and could therefore be responsible for some of the tissue damage seen in chronic asthma. IL-9 has pleiotropic activities on allergic mediators such as mast cells, eosinophils, B cells and epithelial cells, and might be a good target for therapeutic interventions. Finally, chemokines, which can be produced by many cell types from inflamed lungs, play a major role in recruiting the mediators of asthmatic inflammation. Genetic studies have demonstrated that multiple genes are involved in asthma. Several genome wide screens point to chromosome 5q3133 as a major susceptibility locus for asthma and high IgE values. This region includes a cluster of cytokine genes, and genes encoding IL-3, IL-4, IL-5, IL-9, IL-13, granulocyte macrophage colony stimulating factor, and the ß chain of IL-12. Interestingly, for some of these cytokines, a linkage was also established between asthma and their receptor. Another susceptibility locus has been mapped on chromosome 12 in a region that contains other potential candidate cytokine genes, including the gene encoding interferon
, the prototypical TH1 cytokine with inhibitory activities for TH2 lymphocytes. Taken together, both experimental and genetic studies point to TH2 cytokines, such as IL-4, IL-13, IL-5, and IL-9, as important targets for therapeutic applications in patients with asthma.
Key Words:
asthma cytokines interleukins treatment of asthma interferon 
This article has been cited by other articles:
![]() |
A. S. Sabnis, C. A. Reilly, J. M. Veranth, and G. S. Yost Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L194 - L200. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Chen, M. Petrus, B. R. Bryant, V. Phuc Nguyen, M. Stamer, C. K. Goldman, R. Bamford, J. C. Morris, J. E. Janik, and T. A. Waldmann Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation of primary adult T-cell leukemia cells by a paracrine mechanism Blood, May 15, 2008; 111(10): 5163 - 5172. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. A. Hanania Targeting Airway Inflammation in Asthma: Current and Future Therapies Chest, April 1, 2008; 133(4): 989 - 998. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. G. P. Guedes, J. A. Jude, J. Paulin, H. Kita, F. E. Lund, and M. S. Kannan Role of CD38 in TNF-{alpha}-induced airway hyperresponsiveness Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L290 - L299. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Latzin, D. Hartl, N. Regamey, U. Frey, M. H. Schoeni, and C. Casaulta Comparison of serum markers for allergic bronchopulmonary aspergillosis in cystic fibrosis Eur. Respir. J., January 1, 2008; 31(1): 36 - 42. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Zindler, N. Gehrke, C. Luft, S. Reuter, C. Taube, S. Finotto, A. B. Reske-Kunz, and S. Sudowe Divergent Effects of Biolistic Gene Transfer in a Mouse Model of Allergic Airway Inflammation Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 38 - 46. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. N. Gomperts, L. J. Kim, S. A. Flaherty, and B. P. Hackett IL-13 Regulates Cilia Loss and foxj1 Expression in Human Airway Epithelium Am. J. Respir. Cell Mol. Biol., September 1, 2007; 37(3): 339 - 346. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Swaisgood, M. A. Aronica, S. Swaidani, and E. F. Plow Plasminogen Is an Important Regulator in the Pathogenesis of a Murine Model of Asthma Am. J. Respir. Crit. Care Med., August 15, 2007; 176(4): 333 - 342. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. van den Brule, J. Heymans, X. Havaux, J.-C. Renauld, D. Lison, F. Huaux, and O. Denis Profibrotic Effect of IL-9 Overexpression in a Model of Airway Remodeling Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 202 - 209. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Harada, K. Nakashima, T. Hirota, M. Shimizu, S. Doi, K. Fujita, T. Shirakawa, T. Enomoto, M. Yoshikawa, H. Moriyama, et al. Functional Polymorphism in the Suppressor of Cytokine Signaling 1 Gene Associated with Adult Asthma Am. J. Respir. Cell Mol. Biol., April 1, 2007; 36(4): 491 - 496. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Liu, T. Tazzeo, and L. J. Janssen Isoprostane-induced airway hyperresponsiveness is dependent on internal Ca2+ handling and Rho/ROCK signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1177 - L1184. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Zareie, P. Fabbrini, L. H.P. Hekking, E. D. Keuning, P. M. ter Wee, R. H.J. Beelen, and J. van den Born Novel Role for Mast Cells in Omental Tissue Remodeling and Cell Recruitment in Experimental Peritoneal Dialysis J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3447 - 3457. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Klein, S. Klein-Hessling, A. Palmetshofer, E. Serfling, C. Tertilt, T. Bopp, V. Heib, M. Becker, C. Taube, H. Schild, et al. Specific and Redundant Roles for NFAT Transcription Factors in the Expression of Mast Cell-Derived Cytokines J. Immunol., November 15, 2006; 177(10): 6667 - 6674. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-N. Wu, C.-W. Chen, S.-F. Liou, J.-L. Yeh, H.-H. Chung, and I.-J. Chen Inhibition of Proinflammatory Tumor Necrosis Factor-{alpha}-Induced Inducible Nitric-Oxide Synthase by Xanthine-Based 7-[2-[4-(2-Chlorobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine (KMUP-1) and 7-[2-[4-(4-Nitrobenzene)piperazinyl]ethyl]-1, 3-dimethylxanthine (KMUP-3) in Rat Trachea: The Involvement of Soluble Guanylate Cyclase and Protein Kinase G Mol. Pharmacol., September 1, 2006; 70(3): 977 - 985. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Sato, H. Kawashima, S. Kuboshima, K. Watanabe, Y. Kashiwagi, K. Takekuma, and A. Hoshika Combined Treatment of Steroids and Cyclosporine in Kimura Disease Pediatrics, September 1, 2006; 118(3): e921 - e923. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Ishikawa, T. Yoshimoto, and K. Nakanishi Contribution of IL-18-induced innate T cell activation to airway inflammation with mucus hypersecretion and airway hyperresponsiveness Int. Immunol., June 1, 2006; 18(6): 847 - 855. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Rajagopalan, K. Iijima, M. Singh, H. Kita, R. Patel, and C. S. David Intranasal Exposure to Bacterial Superantigens Induces Airway Inflammation in HLA Class II Transgenic Mice Infect. Immun., February 1, 2006; 74(2): 1284 - 1296. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Fischer, J. R. McGhee, H. L. Vu, T. P. Atkinson, R. J. Jackson, D. Tome, and P. N. Boyaka Oral and Nasal Sensitization Promote Distinct Immune Responses and Lung Reactivity in a Mouse Model of Peanut Allergy Am. J. Pathol., December 1, 2005; 167(6): 1621 - 1630. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Candiano, M. Bruschi, N. Pedemonte, E. Caci, S. Liberatori, L. Bini, C. Pellegrini, M. Vigano, B. J. O'Connor, T. H. Lee, et al. Gelsolin Secretion in Interleukin-4-treated Bronchial Epithelia and in Asthmatic Airways Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1090 - 1096. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Rangasamy, J. Guo, W. A. Mitzner, J. Roman, A. Singh, A. D. Fryer, M. Yamamoto, T. W. Kensler, R. M. Tuder, S. N. Georas, et al. Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice J. Exp. Med., July 5, 2005; 202(1): 47 - 59. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Knoops, J. Louahed, J. Van Snick, and J.-C. Renauld IL-9 Promotes but Is Not Necessary for Systemic Anaphylaxis J. Immunol., July 1, 2005; 175(1): 335 - 341. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Deshpande, T. A. White, S. Dogan, T. F. Walseth, R. A. Panettieri, and M. S. Kannan CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle Am J Physiol Lung Cell Mol Physiol, May 1, 2005; 288(5): L773 - L788. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Baelder, B. Fuchs, W. Bautsch, J. Zwirner, J. Kohl, H. G Hoymann, T. Glaab, V. Erpenbeck, N. Krug, and A. Braun Pharmacological Targeting of Anaphylatoxin Receptors during the Effector Phase of Allergic Asthma Suppresses Airway Hyperresponsiveness and Airway Inflammation J. Immunol., January 15, 2005; 174(2): 783 - 789. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Revets, G. Pynaert, J. Grooten, and P. De Baetselier Lipoprotein I, a TLR2/4 Ligand Modulates Th2-Driven Allergic Immune Responses J. Immunol., January 15, 2005; 174(2): 1097 - 1103. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Arras, J. Louahed, J.-F. Heilier, M. Delos, F. Brombacher, J.-C. Renauld, D. Lison, and F. Huaux IL-9 Protects against Bleomycin-Induced Lung Injury: Involvement of Prostaglandins Am. J. Pathol., January 1, 2005; 166(1): 107 - 115. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Suzuki, E. Masini, C. Mazzocca, S. Cuzzocrea, A. Ciampa, H. Suzuki, and D. Bani Inhibition of Poly(ADP-Ribose) Polymerase Prevents Allergen-Induced Asthma-Like Reaction in Sensitized Guinea Pigs J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 1241 - 1248. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Chiba, T. Kusakabe, and S. Kimura Decreased expression of uteroglobin-related protein 1 in inflamed mouse airways is mediated by IL-9 Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1193 - L1198. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Hata, T. Yoshimoto, N. Hayashi, T. Hada, and K. Nakanishi IL-18 together with anti-CD3 antibody induces human Th1 cells to produce Th1- and Th2-cytokines and IL-8 Int. Immunol., December 1, 2004; 16(12): 1733 - 1739. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. S. Rana, M. A. Mittleman, J. Sheikh, F. B. Hu, J. E. Manson, G. A. Colditz, F. E. Speizer, R. G. Barr, and C. A. Camargo Jr Chronic Obstructive Pulmonary Disease, Asthma, and Risk of Type 2 Diabetes in Women Diabetes Care, October 1, 2004; 27(10): 2478 - 2484. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. S. Gounni, Q. Hamid, S. M. Rahman, J. Hoeck, J. Yang, and L. Shan IL-9-Mediated Induction of Eotaxin1/CCL11 in Human Airway Smooth Muscle Cells J. Immunol., August 15, 2004; 173(4): 2771 - 2779. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Claveau, S. L. Chen, S. O'Keefe, D. M. Zaller, A. Styhler, S. Liu, Z. Huang, D. W. Nicholson, and J. A. Mancini Preferential Inhibition of T Helper 1, but Not T Helper 2, Cytokines in Vitro by L-826,141 [4-{2-(3,4-Bisdifluromethoxyphenyl)-2-{4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-phenyl]-ethyl}-3-methylpyridine-1-oxide], a Potent and Selective Phosphodiesterase 4 Inhibitor J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 752 - 760. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. A. Deshpande, S. Dogan, T. F. Walseth, S. M. Miller, Y. Amrani, R. A. Panettieri, and M. S. Kannan Modulation of Calcium Signaling by Interleukin-13 in Human Airway Smooth Muscle: Role of CD38/Cyclic Adenosine Diphosphate Ribose Pathway Am. J. Respir. Cell Mol. Biol., July 1, 2004; 31(1): 36 - 42. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. Cagnoni, S. Oddera, J. Giron-Michel, A. M. Riccio, S. Olsson, P. Dellacasa, G. Melioli, G. W. Canonica, and B. Azzarone CD40 on Adult Human Airway Epithelial Cells: Expression and Proinflammatory Effects J. Immunol., March 1, 2004; 172(5): 3205 - 3214. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Sugimoto, Y. Ishikawa, T. Yoshimoto, N. Hayashi, J. Fujimoto, and K. Nakanishi Interleukin 18 Acts on Memory T Helper Cells Type 1 to Induce Airway Inflammation and Hyperresponsiveness in a Naive Host Mouse J. Exp. Med., February 17, 2004; 199(4): 535 - 545. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. K. Lundy, A. A. Berlin, and N. W. Lukacs Interleukin-12-Independent Down-Modulation of Cockroach Antigen-Induced Asthma in Mice by Intranasal Exposure to Bacterial Lipopolysaccharide Am. J. Pathol., November 1, 2003; 163(5): 1961 - 1968. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Burke Genomics as a Probe for Disease Biology N. Engl. J. Med., September 4, 2003; 349(10): 969 - 974. [Full Text] [PDF] |
||||
![]() |
A. Buske-Kirschbaum, K. von Auer, S. Krieger, S. Weis, W. Rauh, and D. Hellhammer Blunted Cortisol Responses to Psychosocial Stress in Asthmatic Children: A General Feature of Atopic Disease? Psychosom Med, September 1, 2003; 65(5): 806 - 810. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Chen, O. Tliba, C. R. Van Besien, R. A. Panettieri Jr., and Y. Amrani Selected Contribution: TNF-{alpha} modulates murine tracheal rings responsiveness to G-protein-coupled receptor agonists and KCl J Appl Physiol, August 1, 2003; 95(2): 864 - 872. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Baraldo, D. S. Faffe, P. E. Moore, T. Whitehead, M. McKenna, E. S. Silverman, R. A. Panettieri Jr., and S. A. Shore Interleukin-9 influences chemokine release in airway smooth muscle: role of ERK Am J Physiol Lung Cell Mol Physiol, June 1, 2003; 284(6): L1093 - L1102. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Bishop and C. M. Lloyd CC Chemokine Ligand 1 Promotes Recruitment of Eosinophils But Not Th2 Cells During the Development of Allergic Airways Disease J. Immunol., May 1, 2003; 170(9): 4810 - 4817. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Gilliet, V. Soumelis, N. Watanabe, S. Hanabuchi, S. Antonenko, R. de Waal-Malefyt, and Y.-J. Liu Human Dendritic Cells Activated by TSLP and CD40L Induce Proallergic Cytotoxic T Cells J. Exp. Med., April 21, 2003; 197(8): 1059 - 1063. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Iwata, K. Nishio, R. K. Winn, E. Y. Chi, W. R. Henderson Jr., and J. M. Harlan A Broad-Spectrum Caspase Inhibitor Attenuates Allergic Airway Inflammation in Murine Asthma Model J. Immunol., March 15, 2003; 170(6): 3386 - 3391. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. D. Vermeer, R. Harson, L. A. Einwalter, T. Moninger, and J. Zabner Interleukin-9 Induces Goblet Cell Hyperplasia during Repair of Human Airway Epithelia Am. J. Respir. Cell Mol. Biol., March 1, 2003; 28(3): 286 - 295. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Smith, S. Brookes-Fazakerley, L. E. Donnelly, P. J. Barnes, M. S. Barnette, and M. A. Giembycz Ubiquitous expression of phosphodiesterase 7A in human proinflammatory and immune cells Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L279 - L289. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Pilette, Y. Ouadrhiri, J. Van Snick, J-C. Renauld, P. Staquet, J-P. Vaerman, and Y. Sibille Oxidative burst in lipopolysaccharide-activated human alveolar macrophages is inhibited by interleukin-9 Eur. Respir. J., November 1, 2002; 20(5): 1198 - 1205. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. McMillan, B. Bishop, M. J. Townsend, A. N. McKenzie, and C. M. Lloyd The Absence of Interleukin 9 Does Not Affect the Development of Allergen-induced Pulmonary Inflammation nor Airway Hyperreactivity J. Exp. Med., January 7, 2002; 195(1): 51 - 57. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
| Journal of Clinical Pathology | Molecular Pathology |