Background: Airway eosinophilia is frequently observed during acute exacerbation of asthma. Interleukin-5 (IL-5) and eotaxin are directly involved in the airway eosinophilia found in persistent asthma. Interrelation between these cytokines is expected to occur in acute exacerbation of asthma. Thus, we evaluated the relevance of interaction between eotaxin and IL-5 in the airway inflammation of acute exacerbation. Methods: We measured the number of inflammatory cells and the amount of eotaxin and IL-5 in sputum from 22 healthy subjects, 21 asthmatics with acute exacerbation and 16 patients with mild persistent asthma, and reassessed these values in 7 subjects with acute exacerbation after 7 days’ treatment with systemic steroid (2 mg/kg/day). Sources of IL-5 and eotaxin were investigated by immunohistochemical staining of sputum cells of 4 cases from each group. Results: Both IL-5 and eotaxin levels were higher in patients with acute exacerbation of asthma than in patients with persistent asthma and normal subjects. IL-5 and eotaxin levels were significantly correlated with eosinophil percentages in mild persistent asthma. Eotaxin staining was found mainly on macrophages and occasionally on eosinophils. Steroid treatment markedly decreased eosinophil percentages and IL-5 levels within 7 days but did not alter eotaxin levels. Conclusions: Both IL-5 and eotaxin are associated with acute exacerbation of asthma. IL-5 rather than eotaxin is effectively decreased by the inhibitory effect of steroid in acute exacerbation.

Keywords:
Asthma exacerbation, Interleukin-5, Eotaxin, Sputum eosinophils
1.
Bousquet J, Chanez P, Lacoste JY, Barneon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P, Michel P-B: Eosinophilic inflammation in asthma. N Engl J Med 1990;323:1033–1039.
2.
Azzawi M, Johnston PW, Majumdar S, Kay AB, Jeffery PK: T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis. Am Rev Respir Dis 1992;145:1477–1482.
3.
Fahy JV, Kim KW, Liu J, Boushey HA: Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol 1995;95:843–852.
4.
Pizzichini MM, Pizzichini E, Clelland L, Efthimadis A, Mahony J, Hargreave FE: Sputum in severe exacerbation of asthma: Kinetics of inflammatory indices after prednisone treatment. Am J Respir Crit Care Med 1997;155:1501–1508.
5.
Tillie-Leblond I, Hammad H, Desurmont S, Pugin J, Wallaert B, Tonnel AB, Gosset P: CC chemokines and interleukin-5 in bronchial lavage fluid from patients with status asthmaticus: Potential implication in eosinophil recruitment. Am J Respir Crit Care Med 2000;162:586–592.
6.
Ordoňez CL, Shaughnessy TE, Matthay MA, Fahy JV: Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance. Am J Respir Crit Care Med 2000;161:1185–1190.
7.
Twaddel SH, Gibson PG, Carty K, Wooley KL, Henry RL: Assessment of airway inflammation in children with acute asthma using induced sputum. Eur Respir J 1996;9:2104–2108.
8.
Gibson PG, Norsila MZ, Fakes K, Simpson J, Henry RL: Pattern of airway inflammation and its determinants in children with acute severe asthma. Pediatr Pulmonol 1999;28:261–270.
9.
Norzila MZ, Fakes K, Henry RL, Simpson J, Gibson PG: Interleukin-8 secretion and neutrophil recruitment accompanies induced sputum eosinophil activation in children with acute asthma. Am J Respir Crit Care Med 2000;161:769–774.
10.
Lalani T, Simmons RK, Ahmed AR: Biology of IL-5 in health and disease. Ann Allergy Asthma Immunol 1999;82:317–332.
11.
Hamid Q, Azzawi M, Ying S, Moqbel R, Wardlaw AJ, Corrigan CJ, Bradley B, Durham SR, Collins JV, Jeffery PK, Quint DJ, Kay AB: Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest 1991;87:1541–1546.
12.
Ohnishi T, Kita H, Weiler D, Sur S, Sedgwick JB, Calhoun WJ, Busse WW, Abrams JS, Gleich GJ: IL-5 is the predominant eosinophil-active cytokine in the antigen-induced pulmonary late-phase reaction. Am Rev Respir Dis 1993;147:901–907.
13.
Keatings VM, O’Connor BJ, Wright LG, Huston DP, Corrigan CJ, Barnes PJ: Late response to allergen is associated with increased concentrations of tumor necrosis factor-alpha and IL-5 in induced sputum. J Allergy Clin Immunol 1997;99:693–698.
14.
Øymar K, Elsayed S, Bjerknes R: Serum eosinophil cationic protein and interleukin-5 in children with bronchial asthma and acute bronchiolitis. Pediatr Allergy Immunol 1996;7:180–186.
15.
Ponath PD, Qin S, Post TW, Wang J, Wu L, Gerard NP, Newman W, Gerard C, Mackay CR: Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med 1996;183:2437–2448.
16.
Ying S, Robinson DS, Meng Q, Rottman J, Kennedy R, Ringler DJ, Mackay CR, Daugherty BA, Springer MS, Durham SR, Williams TJ, Kay AB: Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant colocalization of eotaxin mRNA to bronchial epithelial and endothelial cells. Eur J Immunol 1997;27:3507–3516.
17.
Lamkhioued B, Renzi PM, Abi-Younes S, Garcia-Zepada EA, Allakhverdi Z, Ghaffar O, Rothenberg MD, Luster AD, Hamid Q: Increased expression of eotaxin in bronchial alveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation. J Immunol 1997;159:4593–4601.
18.
Ying S, Meng Q, Zeibecoglou K, Robinson DS, Macfarlane A, Humbert M, Kay AB: Eosinophil chemotactic chemokines eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4, and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (Intrinsic) asthmatics. J Immunol 1999;163:6321–6329.
19.
Taha RA, Minshall EM, Miotto D, Shimbara A, Luster A, Hogg JC, Hamid QA: Eotaxin and MCP-4 mRNA expression in small airways of asthmatic and nonasthmatic individuals. J Allergy Clin Immunol 1999;103:476–483.
20.
Yamada H, Yamaguchi M, Yamamoto K, Nakajima T, Hirai K, Morita Y, Sano Y, Yamada H: Eotaxin in induced sputum of asthmatics: Relationship with eosinophils and eosinophil cationic protein in sputum. Allergy 2000;55:392–397.
21.
Zeibecoglou K, Macfarlane AJ, Ying S, Meng Q, Pavord I, Barnes NC, Robinson DS, Kay AB: Increase in eotaxin-positive cells in induced sputum from atopic asthmatic subjects after inhalational allergen challenge. Allergy 1999;54:730–735.
22.
Stirling RG, van Rensen EL, Barnes PJ, Chung KF: Interleukin-5 induces CD34(+) eosinophil progenitor mobilization and eosinophil CCR3 expression in asthma. Am J Respir Crit Care Med 2001;164:1403–1409
23.
van Rensen ELJ, Stirling RG, Scheerens J, Staples K, Sterk PJ, Barnes PJ, Chung KF: Evidence for systemic rather than pulmonary effects of interleukin-5 administration in asthma. Thorax 2001;56:935–940.
24.
Pin I, Gibson PG, Kolendowicz R, Girgis-Gabardo A, Denburg JA, Hargreave FE, Dolovich J: Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax 1992;47:25–29.
25.
Juniper EF, Cockcroft DW, Hargreave FE: Histamine and Methacholine Inhalation Tests: A Laboratory Tidal Breathing Protocol, ed 2. Lund, Astra Draco, 1994.
26.
Park CS, Kim YY, Kang SY: Collection between RAST and skin test for inhalant offending allergens. J Korean Soc Allergol 1983;3:1–9.
27.
Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, November 1986. Am Rev Respir Dis 1987;136:225–244.
28.
Mould AW, Matthaei KI, Young LG, Foster PS: Relationship between interleukin-5 and eotaxin in regulating blood and tissue eosinophilia in mice. J Clin Invest 1997;99:1064–1071.
29.
Wang J, Palmer K, Lotvall J, Milan S, Lei X-F, Matthaei KI, Gauldie J, Inman MD, Jordana M, Xing Z: Circulating, but not local lung, IL-5 is required for the development of antigen-induced airways eosinophilia. J Clin Invest 1998;102:1132–1141.
30.
Kudlacz E, Whitney C, Andresen C, Conklyn M: Function effects of eotaxin are selectively upregulated on IL-5 transgenic mouse eosinophils. Inflammation 2002;26:111–119.
31.
Han SJ, Kim JH, Noh YJ, Chang HS, Kim CS, Kim K-S, Ki SY, Park CS, Chung IY: Interleukin-5 downregulates tumor necrosis factor-induced eotaxin messenger RNA expression in eosinophils. Am J Respir Cell Mol Biol 1999;21:303–310.
32.
Gemou-Engesaeth V, Bush A, Kay AB, Hamid Q, Corrigan CJ: Inhaled glucocorticoid therapy of childhood asthma is associated with reduced peripheral blood T cell activation and ‘Th2-type’ cytokine mRNA expression. Pediatrics 1997;99:695–703.
33.
Lilly CM, Nakamura H, Kesselman H, Nagler-Anderson C, Asano K, Garcia-Zepeda EA, Rothenberg ME, Drazen JM, Luster AD: Expression of eotaxin by human lung epithelial cells: Induction by cytokines and inhibition by glucocorticoids. J Clin Invest 1997;99:1767–1773.
34.
Humbles AA, Conroy DM, Marleau S, Rankin AM, Palframan RT, Proudfoot AEI, Wells TNC, Li D, Jefferry PK, Griffiths-Johnson DA, Williams TJ, Jose PJ: Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: Analysis in a guinea pig model in vivo. J Exp Med 1997;186:601–612.
© 2003 S. Karger AG, Basel
2003
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.