Airway neutrophils and interleukin-17

It is well known that exacerbations of obstructive airways disease such as asthma and chronic obstructive pulmonary disease are associated with an increased number of neutrophils in the airways. However, the mechanisms behind this phenomenon are poorly understood. There is in vivo experimental evidence that the number of airway neutrophils is controlled by certain T-lymphocytes, but the mediators responsible for this lymphocyte-related neutrophilia have not yet been identified. In this review, novel evidence that the T-lymphocyte-related cytokine interleukin (IL)-17 can link the activation of certain T-lymphocytes to the recruitment and activation of airway neutrophils is described. The IL-17-induced neutrophil recruitment is mediated via induced CXC chemokine release through steroid-sensitive mechanisms and is modulated by release of endogenous tachykinins. These effects of IL-17 are potentiated by other pro-inflammatory cytokines such as (IL-1beta) and tumour necrosis factor-alpha. Clinical studies are needed to evaluate whether or not targeting these mechanisms can provide a useful pharmacotherapeutical approach against exaggerated mobilization of neutrophils in obstructive airways disease.

This article has been cited by other articles:

				V. Brucklacher-Waldert, K. Stuerner, M. Kolster, J. Wolthausen, and E. Tolosa Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis Brain, November 23, 2009; (2009) awp289v1. [Abstract] [Full Text] [PDF]

				Y.-S. Kim, S.-W. Hong, J.-P. Choi, T.-S. Shin, H.-G. Moon, E.-J. Choi, S. G. Jeon, S.-Y. Oh, Y. S. Gho, Z. Zhu, et al. Vascular Endothelial Growth Factor Is a Key Mediator in the Development of T Cell Priming and Its Polarization to Type 1 and Type 17 T Helper Cells in the Airways J. Immunol., October 15, 2009; 183(8): 5113 - 5120. [Abstract] [Full Text] [PDF]

				P. L. Simonian, C. L. Roark, F. Wehrmann, A. K. Lanham, F. Diaz del Valle, W. K. Born, R. L. O'Brien, and A. P. Fontenot Th17-Polarized Immune Response in a Murine Model of Hypersensitivity Pneumonitis and Lung Fibrosis J. Immunol., January 1, 2009; 182(1): 657 - 665. [Abstract] [Full Text] [PDF]

				F. Y. Yue, A. Merchant, C. M. Kovacs, M. Loutfy, D. Persad, and M. A. Ostrowski Virus-Specific Interleukin-17-Producing CD4+ T Cells Are Detectable in Early Human Immunodeficiency Virus Type 1 Infection J. Virol., July 1, 2008; 82(13): 6767 - 6771. [Abstract] [Full Text] [PDF]

				A. Linden A Role for the Cytoplasmic Adaptor Protein Act1 in Mediating IL-17 Signaling Sci. Signal., August 7, 2007; 2007(398): re4 - re4. [Abstract] [Full Text] [PDF]

				B. M. Vanaudenaerde, L. J. Dupont, W. A. Wuyts, E. K. Verbeken, I. Meyts, D. M. Bullens, E. Dilissen, L. Luyts, D. E. Van Raemdonck, and G. M. Verleden The role of interleukin-17 during acute rejection after lung transplantation. Eur. Respir. J., April 1, 2006; 27(4): 779 - 787. [Abstract] [Full Text] [PDF]

				Y. Maezawa, H. Nakajima, K. Suzuki, T. Tamachi, K. Ikeda, J.-i. Inoue, Y. Saito, and I. Iwamoto Involvement of TNF Receptor-Associated Factor 6 in IL-25 Receptor Signaling J. Immunol., January 15, 2006; 176(2): 1013 - 1018. [Abstract] [Full Text] [PDF]

				S. A. Khader, J. E. Pearl, K. Sakamoto, L. Gilmartin, G. K. Bell, D. M. Jelley-Gibbs, N. Ghilardi, F. deSauvage, and A. M. Cooper IL-23 Compensates for the Absence of IL-12p70 and Is Essential for the IL-17 Response during Tuberculosis but Is Dispensable for Protection and Antigen-Specific IFN-{gamma} Responses if IL-12p70 Is Available J. Immunol., July 15, 2005; 175(2): 788 - 795. [Abstract] [Full Text] [PDF]

				F. McAllister, A. Henry, J. L. Kreindler, P. J. Dubin, L. Ulrich, C. Steele, J. D. Finder, J. M. Pilewski, B. M. Carreno, S. J. Goldman, et al. Role of IL-17A, IL-17F, and the IL-17 Receptor in Regulating Growth-Related Oncogene-{alpha} and Granulocyte Colony-Stimulating Factor in Bronchial Epithelium: Implications for Airway Inflammation in Cystic Fibrosis J. Immunol., July 1, 2005; 175(1): 404 - 412. [Abstract] [Full Text] [PDF]

				K. Ikeda, H. Nakajima, K. Suzuki, S.-i. Kagami, K. Hirose, A. Suto, Y. Saito, and I. Iwamoto Mast cells produce interleukin-25 upon Fcepsilon RI-mediated activation Blood, May 1, 2003; 101(9): 3594 - 3596. [Abstract] [Full Text] [PDF]

				S. Ferretti, O. Bonneau, G. R. Dubois, C. E. Jones, and A. Trifilieff IL-17, Produced by Lymphocytes and Neutrophils, Is Necessary for Lipopolysaccharide-Induced Airway Neutrophilia: IL-15 as a Possible Trigger J. Immunol., February 15, 2003; 170(4): 2106 - 2112. [Abstract] [Full Text] [PDF]

				S. Aggarwal, N. Ghilardi, M.-H. Xie, F. J. de Sauvage, and A. L. Gurney Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17 J. Biol. Chem., January 10, 2003; 278(3): 1910 - 1914. [Abstract] [Full Text] [PDF]

				J. Maertzdorf, A. D. M. E. Osterhaus, and G. M. G. M. Verjans IL-17 Expression in Human Herpetic Stromal Keratitis: Modulatory Effects on Chemokine Production by Corneal Fibroblasts J. Immunol., November 15, 2002; 169(10): 5897 - 5903. [Abstract] [Full Text] [PDF]

				C. E. Jones and K. Chan Interleukin-17 Stimulates the Expression of Interleukin-8, Growth-Related Oncogene-alpha , and Granulocyte-Colony-Stimulating Factor by Human Airway Epithelial Cells Am. J. Respir. Cell Mol. Biol., June 1, 2002; 26(6): 748 - 753. [Abstract] [Full Text] [PDF]

				M. Laan, L. Palmberg, K. Larsson, and A. Linden Free, soluble interleukin-17 protein during severe inflammation in human airways Eur. Respir. J., March 1, 2002; 19(3): 534 - 537. [Abstract] [Full Text] [PDF]

				S. Aggarwal and A. L. Gurney IL-17: prototype member of an emerging cytokine family J. Leukoc. Biol., January 1, 2002; 71(1): 1 - 8. [Abstract] [Full Text] [PDF]

				G. Pan, D. French, W. Mao, M. Maruoka, P. Risser, J. Lee, J. Foster, S. Aggarwal, K. Nicholes, S. Guillet, et al. Forced Expression of Murine IL-17E Induces Growth Retardation, Jaundice, a Th2-Biased Response, and Multiorgan Inflammation in Mice J. Immunol., December 1, 2001; 167(11): 6559 - 6567. [Abstract] [Full Text] [PDF]

				J.-P. LAVOIE, K. MAGHNI, M. DESNOYERS, R. TAHA, J. G. MARTIN, and Q. A. HAMID Neutrophilic Airway Inflammation in Horses with Heaves Is Characterized by a Th2-type Cytokine Profile Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1410 - 1413. [Abstract] [Full Text] [PDF]

				T. Starnes, M. J. Robertson, G. Sledge, S. Kelich, H. Nakshatri, H. E. Broxmeyer, and R. Hromas Cutting Edge: IL-17F, a Novel Cytokine Selectively Expressed in Activated T Cells and Monocytes, Regulates Angiogenesis and Endothelial Cell Cytokine Production J. Immunol., October 15, 2001; 167(8): 4137 - 4140. [Abstract] [Full Text] [PDF]

				P. Ye, P. B. Garvey, P. Zhang, S. Nelson, G. Bagby, W. R. Summer, P. Schwarzenberger, J. E. Shellito, and J. K. Kolls Interleukin-17 and Lung Host Defense against Klebsiella pneumoniae Infection Am. J. Respir. Cell Mol. Biol., September 1, 2001; 25(3): 335 - 340. [Abstract] [Full Text] [PDF]