ORIGINAL ARTICLE

Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema

M Tanino, T Betsuyaku, K Takeyabu, Y Tanino, E Yamaguchi, K Miyamoto, M Nishimura

First Department of Medicine, Hokkaido University School of Medicine, Kita-ku, Sapporo, 060–8638, Japan

Correspondence to:
Correspondence to:
Dr M Tanino, First Department of Medicine, Hokkaido University School of Medicine, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan;
tanino{at}med.hokudai.ac.jp

Background: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid.

Methods: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B₄ (LTB₄) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1) which are predominantly chemotactic for mononuclear leucocytes.

Results: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.7 and 12.2 pg/ml, respectively, p<0.01). In addition, the levels of IL-8 and neutrophil elastase-₁ protease inhibitor complex in BAL fluid were significantly correlated (r=0.65, p<0.01). There was no difference in either the release of IL-8 from cultured alveolar macrophages at 24 hours or the expression of IL-8 messenger RNA of alveolar macrophages in the two groups of current smokers with and without emphysema.

Conclusion: An accelerated response of IL-8 to chronic smoking is a factor that characterises those smokers who are susceptible to pulmonary emphysema, although the cellular source of IL-8 remains to be determined.

Keywords: pulmonary emphysema; interleukin-8; neutrophil; smoking

Abbreviations: ENA-78, epithelial neutrophil activating protein 78; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; IL-8, interleukin 8; LTB₄, leukotriene B₄; MCP-1, monocyte chemoattractant protein 1; MIP-1, macrophage inflammatory protein 1; NE-₁PI, neutrophil elastase-₁ protease inhibitor complex; TLCO, carbon monoxide transfer factor; VC, vital capacity

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Di Stefano, A, Caramori, G, Gnemmi, I, Contoli, M, Bristot, L, Capelli, A, Ricciardolo, F L M, Magno, F, D'Anna, S E., Zanini, A, Carbone, M, Sabatini, F, Usai, C, Brun, P, Chung, K F, Barnes, P J, Papi, A, Adcock, I M, Balbi, B (2009). Association of increased CCL5 and CXCL7 chemokine expression with neutrophil activation in severe stable COPD. Thorax 64: 968-975 [Abstract] [Full Text]  
• Li, Z., Alam, S., Wang, J., Sandstrom, C. S., Janciauskiene, S., Mahadeva, R. (2009). Oxidized {alpha}1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema. Am. J. Physiol. Lung Cell. Mol. Physiol. 297: L388-L400 [Abstract] [Full Text]  
• Finney-Hayward, T. K., Bahra, P., Li, S., Poll, C. T., Nicholson, A. G., Russell, R. E. K., Ford, P. A., Westwick, J., Fenwick, P. S., Barnes, P. J., Donnelly, L. E. (2009). Leukotriene B4 release by human lung macrophages via receptor- not voltage-operated Ca2+ channels. Eur Respir J 33: 1105-1112 [Abstract] [Full Text]  
• Sethi, S., Murphy, T. F. (2008). Infection in the Pathogenesis and Course of Chronic Obstructive Pulmonary Disease. NEJM 359: 2355-2365 [Full Text]  
• Myrtek, D., Muller, T., Geyer, V., Derr, N., Ferrari, D., Zissel, G., Durk, T., Sorichter, S., Luttmann, W., Kuepper, M., Norgauer, J., Di Virgilio, F., Virchow, J. C. Jr, Idzko, M. (2008). Activation of Human Alveolar Macrophages via P2 Receptors: Coupling to Intracellular Ca2+ Increases and Cytokine Secretion. J. Immunol. 181: 2181-2188 [Abstract] [Full Text]  
• Kim, V., Rogers, T. J., Criner, G. J. (2008). New Concepts in the Pathobiology of Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 5: 478-485 [Abstract] [Full Text]  
• Sethi, S., Wrona, C., Eschberger, K., Lobbins, P., Cai, X., Murphy, T. F. (2008). Inflammatory Profile of New Bacterial Strain Exacerbations of Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 177: 491-497 [Abstract] [Full Text]  
• Yamagata, T., Sugiura, H., Yokoyama, T., Yanagisawa, S., Ichikawa, T., Ueshima, K., Akamatsu, K., Hirano, T., Nakanishi, M., Yamagata, Y., Matsunaga, K., Minakata, Y., Ichinose, M. (2007). Overexpression of CD-11b and CXCR1 on Circulating Neutrophils: Its Possible Role in COPD. Chest 132: 890-899 [Abstract] [Full Text]  
• Chapman, R. W., Minnicozzi, M., Celly, C. S., Phillips, J. E., Kung, T. T., Hipkin, R. W., Fan, X., Rindgen, D., Deno, G., Bond, R., Gonsiorek, W., Billah, M. M., Fine, J. S., Hey, J. A. (2007). A Novel, Orally Active CXCR1/2 Receptor Antagonist, Sch527123, Inhibits Neutrophil Recruitment, Mucus Production, and Goblet Cell Hyperplasia in Animal Models of Pulmonary Inflammation. J. Pharmacol. Exp. Ther. 322: 486-493 [Abstract] [Full Text]  
• Lapperre, T. S., Willems, L. N. A., Timens, W., Rabe, K. F., Hiemstra, P. S., Postma, D. S., Sterk, P. J., the GLUCOLD Study Group, (2007). Small Airways Dysfunction and Neutrophilic Inflammation in Bronchial Biopsies and BAL in COPD. Chest 131: 53-59 [Abstract] [Full Text]  
• Marian, E., Baraldo, S., Visentin, A., Papi, A., Saetta, M., Fabbri, L. M., Maestrelli, P. (2006). Up-Regulated Membrane and Nuclear Leukotriene B4 Receptors in COPD. Chest 129: 1523-1530 [Abstract] [Full Text]  
• O'Donnell, R, Breen, D, Wilson, S, Djukanovic, R (2006). Inflammatory cells in the airways in COPD. Thorax 61: 448-454 [Abstract] [Full Text]  
• Sethi, S., Maloney, J., Grove, L., Wrona, C., Berenson, C. S. (2006). Airway Inflammation and Bronchial Bacterial Colonization in Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 173: 991-998 [Abstract] [Full Text]  
• MacNee, W. (2005). Pathogenesis of Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 2: 258-266 [Abstract] [Full Text]  
• Barnes, P. J., Stockley, R. A. (2005). COPD: current therapeutic interventions and future approaches. Eur Respir J 25: 1084-1106 [Abstract] [Full Text]  
• Berenson, C. S., Murphy, T. F., Wrona, C. T., Sethi, S. (2005). Outer Membrane Protein P6 of Nontypeable Haemophilus influenzae Is a Potent and Selective Inducer of Human Macrophage Proinflammatory Cytokines. Infect. Immun. 73: 2728-2735 [Abstract] [Full Text]  
• Drost, E M, Skwarski, K M, Sauleda, J, Soler, N, Roca, J, Agusti, A, MacNee, W (2005). Oxidative stress and airway inflammation in severe exacerbations of COPD. Thorax 60: 293-300 [Abstract] [Full Text]  
• Stevenson, C. S., Coote, K., Webster, R., Johnston, H., Atherton, H. C., Nicholls, A., Giddings, J., Sugar, R., Jackson, A., Press, N. J., Brown, Z., Butler, K., Danahay, H. (2005). Characterization of cigarette smoke-induced inflammatory and mucus hypersecretory changes in rat lung and the role of CXCR2 ligands in mediating this effect. Am. J. Physiol. Lung Cell. Mol. Physiol. 288: L514-L522 [Abstract] [Full Text]  
• Barnes, P. J. (2004). Mediators of Chronic Obstructive Pulmonary Disease. Pharmacol. Rev. 56: 515-548 [Abstract] [Full Text]  
• Fuke, S., Betsuyaku, T., Nasuhara, Y., Morikawa, T., Katoh, H., Nishimura, M. (2004). Chemokines in Bronchiolar Epithelium in the Development of Chronic Obstructive Pulmonary Disease. Am. J. Respir. Cell Mol. Bio. 31: 405-412 [Abstract] [Full Text]  
• Fujita, M, Ye, Q, Ouchi, H, Nakashima, N, Hamada, N, Hagimoto, N, Kuwano, K, Mason, R J, Nakanishi, Y (2004). Retinoic acid fails to reverse emphysema in adult mouse models. Thorax 59: 224-230 [Abstract] [Full Text]  
• Barnes, P.J., Shapiro, S.D., Pauwels, R.A. (2003). Chronic obstructive pulmonary disease: molecular and cellularmechanisms. Eur Respir J 22: 672-688 [Abstract] [Full Text]  
• Balbi, B. (2003). COPD: Is Chemotaxis the Key?. Chest 123: 983-986 [Full Text]  
• Culpitt, S. V., Rogers, D. F., Shah, P., De Matos, C., Russell, R. E. K., Donnelly, L. E., Barnes, P. J. (2003). Impaired Inhibition by Dexamethasone of Cytokine Release by Alveolar Macrophages from Patients with Chronic Obstructive Pulmonary Disease. Am. J. Respir. Crit. Care Med. 167: 24-31 [Abstract] [Full Text]