Endobronchial secretion of interleukin-13 following local allergen challenge in atopic asthma: relationship to interleukin-4 and eosinophil counts

We investigated the secretion of interleukin (IL)-13 into the airways in 10 mild allergic asthmatics by employing local allergen challenge, and compared the data both to IL-4 levels and eosinophil numbers obtained by bronchoalveolar lavage (BAL). Appropriate allergen or saline were endoscopically instilled into different airway segments, which were lavaged 10 min and 18 h after allergen or sham challenge. IL-4 and IL-13 were measured in unconcentrated BAL fluid using a double sandwich enzymes-linked immunosorbent assay (ELISA). Endobronchial allergen challenge induced a highly significant increase in the numbers of eosinophils after 18 h in the allergen exposed segment. Ten minutes following allergen exposure, low levels of IL-4 and IL-13 could be detected, whilst concentrations of both cytokines were significantly raised 18 h following local allergen exposure. In contrast to IL-4, the concentration of IL-13 strongly correlated with the eosinophil numbers found 18 h post-allergen challenge. The results suggest that interleukin-13 is actively secreted during the late asthmatic response in mild asthmatic subjects. In view of its action on eosinophils and other cell types, we conclude that interleukin-13, in addition to interleukin-4, may play an important role in the pathogenesis of eosinophil-related inflammation, such as bronchial asthma.

This article has been cited by other articles:

				N. M. Heller, X. Qi, I. S. Junttila, K. A. Shirey, S. N. Vogel, W. E. Paul, and A. D. Keegan Type I IL-4Rs Selectively Activate IRS-2 to Induce Target Gene Expression in Macrophages Sci. Signal., December 23, 2008; 1(51): ra17 - ra17. [Abstract] [Full Text] [PDF]

				G. Martin, R. J. O'Connell, A. Z. Pietrzykowski, S. N. Treistman, M. F. Ethier, and J. M. Madison Interleukin-4 activates large-conductance, calcium-activated potassium (BKCa) channels in human airway smooth muscle cells Exp Physiol, July 1, 2008; 93(7): 908 - 918. [Abstract] [Full Text] [PDF]

				S. Y. Thomas, A. Banerji, B. D. Medoff, C. M. Lilly, and A. D. Luster Multiple Chemokine Receptors, Including CCR6 and CXCR3, Regulate Antigen-Induced T Cell Homing to the Human Asthmatic Airway J. Immunol., August 1, 2007; 179(3): 1901 - 1912. [Abstract] [Full Text] [PDF]

				J. Kearley, S. J. McMillan, and C. M. Lloyd Th2-driven, allergen-induced airway inflammation is reduced after treatment with anti Tim-3 antibody in vivo J. Exp. Med., June 11, 2007; 204(6): 1289 - 1294. [Abstract] [Full Text] [PDF]

				A.-L. Andrews, J. W. Holloway, S. T. Holgate, and D. E. Davies IL-4 Receptor {alpha} Is an Important Modulator of IL-4 and IL-13 Receptor Binding: Implications for the Development of Therapeutic Targets. J. Immunol., June 15, 2006; 176(12): 7456 - 7461. [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]

				C. Pilette, J.N. Francis, S.J. Till, and S.R. Durham CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge Eur. Respir. J., June 1, 2004; 23(6): 876 - 884. [Abstract] [Full Text] [PDF]

				N. G. Sandler, M. M. Mentink-Kane, A. W. Cheever, and T. A. Wynn Global Gene Expression Profiles During Acute Pathogen-Induced Pulmonary Inflammation Reveal Divergent Roles for Th1 and Th2 Responses in Tissue Repair J. Immunol., October 1, 2003; 171(7): 3655 - 3667. [Abstract] [Full Text] [PDF]

				V Brown, T J Warke, M D Shields, and M Ennis T cell cytokine profiles in childhood asthma Thorax, April 1, 2003; 58(4): 311 - 316. [Abstract] [Full Text] [PDF]

				M. Inman Do Complex Conditions Require Complex Treatment? Am. J. Respir. Crit. Care Med., January 1, 2003; 167(1): 6 - 6. [Full Text] [PDF]

				J. Mattes, M. Yang, S. Mahalingam, J. Kuehr, D. C. Webb, L. Simson, S. P. Hogan, A. Koskinen, A. N.J. McKenzie, L. A. Dent, et al. Intrinsic Defect in T Cell Production of Interleukin (IL)-13 in the Absence of Both IL-5 and Eotaxin Precludes the Development of Eosinophilia and Airways Hyperreactivity in Experimental Asthma J. Exp. Med., June 3, 2002; 195(11): 1433 - 1444. [Abstract] [Full Text] [PDF]

				S. J. Hirst, M. P. Hallsworth, Q. Peng, and T. H. Lee Selective Induction of Eotaxin Release by Interleukin-13 or Interleukin-4 in Human Airway Smooth Muscle Cells Is Synergistic with Interleukin-1beta and Is Mediated by the Interleukin-4 Receptor alpha -Chain Am. J. Respir. Crit. Care Med., April 15, 2002; 165(8): 1161 - 1171. [Abstract] [Full Text] [PDF]

				T. D. Howard, P. A. Whittaker, A. L. Zaiman, G. H. Koppelman, J. Xu, M. T. Hanley, D. A. Meyers, D. S. Postma, and E. R. Bleecker Identification and Association of Polymorphisms in the Interleukin-13 Gene with Asthma and Atopy in a Dutch Population Am. J. Respir. Cell Mol. Biol., September 1, 2001; 25(3): 377 - 384. [Abstract] [Full Text] [PDF]

				M. Thivierge, J. Stankova, and M. Rola-Pleszczynski IL-13 and IL-4 Up-Regulate Cysteinyl Leukotriene 1 Receptor Expression in Human Monocytes and Macrophages J. Immunol., September 1, 2001; 167(5): 2855 - 2860. [Abstract] [Full Text] [PDF]

				C. M. Fleming, H. He, A. Ciota, D. Perkins, and P. W. Finn Administration of Pentoxifylline During Allergen Sensitization Dissociates Pulmonary Allergic Inflammation from Airway Hyperresponsiveness J. Immunol., August 1, 2001; 167(3): 1703 - 1711. [Abstract] [Full Text] [PDF]

				N. Krug, V. J. Erpenbeck, K. Balke, J. Petschallies, T. Tschernig, J. M. Hohlfeld, and H. Fabel Cytokine Profile of Bronchoalveolar Lavage-Derived CD4+, CD8+, and gamma delta T Cells in People with Asthma after Segmental Allergen Challenge Am. J. Respir. Cell Mol. Biol., July 1, 2001; 25(1): 125 - 131. [Abstract] [Full Text] [PDF]

				F. H. Falcone, H. Haas, and B. F. Gibbs The human basophil: a new appreciation of its role in immune responses Blood, December 15, 2000; 96(13): 4028 - 4038. [Full Text] [PDF]

				D. Serebrisky, A. A. Teper, C.-K. Huang, S.-Y. Lee, T.-F. Zhang, B. H. Schofield, M. Kattan, H. A. Sampson, and X.-M. Li CpG Oligodeoxynucleotides Can Reverse Th2-Associated Allergic Airway Responses and Alter the B7.1/B7.2 Expression in a Murine Model of Asthma J. Immunol., November 15, 2000; 165(10): 5906 - 5912. [Abstract] [Full Text] [PDF]

				M. Zaitsu, Y. Hamasaki, M. Matsuo, A. Kukita, K. Tsuji, M. Miyazaki, R. Hayasaki, E. Muro, S. Yamamoto, I. Kobayashi, et al. New induction of leukotriene A4 hydrolase by interleukin-4 and interleukin-13 in human polymorphonuclear leukocytes Blood, July 15, 2000; 96(2): 601 - 609. [Abstract] [Full Text] [PDF]

				G. Woltmann, C. A. McNulty, G. Dewson, F. A. Symon, and A. J. Wardlaw Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils, but not neutrophils, to human umbilical vein endothelial cells under flow Blood, May 15, 2000; 95(10): 3146 - 3152. [Abstract] [Full Text] [PDF]

				W. R. Henderson Jr., E. Y. Chi, and C. R. Maliszewski Soluble IL-4 Receptor Inhibits Airway Inflammation Following Allergen Challenge in a Mouse Model of Asthma J. Immunol., January 15, 2000; 164(2): 1086 - 1095. [Abstract] [Full Text] [PDF]

				K F Chung and P J Barnes Cytokines in asthma Thorax, September 1, 1999; 54(9): 825 - 857. [Full Text]

				D. Weissflog, C. Kroegel, W. Luttmann, P. R. Grahmann, and J. Hasse Leukocyte Infiltration and Secretion of Cytokines in Pleural Drainage Fluid After Thoracic Surgery: Impaired Cytokine Response in Malignancy and Postoperative Complications Chest, June 1, 1999; 115(6): 1604 - 1610. [Abstract] [Full Text] [PDF]

				K. L. Anderson, P. W. Mathieson, K. M. Gillespie;, M. Wills-Karp, and L. J. Rosenwasser; Polymorphisms Not Found in the IL-13 Gene Promoter Science, May 28, 1999; 284(5419): 1431a - 1431. [Full Text]

				L. Li, Y. Xia, A. Nguyen, Y. H. Lai, L. Feng, T. R. Mosmann, and D. Lo Effects of Th2 Cytokines on Chemokine Expression in the Lung: IL-13 Potently Induces Eotaxin Expression by Airway Epithelial Cells J. Immunol., March 1, 1999; 162(5): 2477 - 2487. [Abstract] [Full Text] [PDF]

				Y. Li, F. E. R. Simons, and K. T. HayGlass Environmental Antigen-Induced IL-13 Responses Are Elevated Among Subjects with Allergic Rhinitis, Are Independent of IL-4, and Are Inhibited by Endogenous IFN-{gamma} Synthesis J. Immunol., December 15, 1998; 161(12): 7007 - 7014. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]

				J. P.B. Viola, A. Kiani, P. T. Bozza, and A. Rao Regulation of Allergic Inflammation and Eosinophil Recruitment in Mice Lacking the Transcription Factor NFAT1: Role of Interleukin-4 (IL-4) and IL-5 Blood, April 1, 1998; 91(7): 2223 - 2230. [Abstract] [Full Text] [PDF]