Background: Elevations of various cytokines, including Th1 and Th2 cytokines, have been reported in the acute phase of Kawasaki syndrome (KS). As interleukin (IL)-18 plays an important role in the Th1 cell response, investigating the relevance of IL-18 in KS should be helpful in determining the pathophysiology of KS. Therefore, we examined the IL-18 values in KS. Methods: Serum IL-18 values were measured by an enzyme-linked immunosorbent assay. Samples were obtained from 41 patients in the acute and subacute phase of KS, 35 age-matched febrile controls and 13 afebrile controls. Results: No difference was observed in the values of white blood cell counts or C-reactive protein between acute-phase KS patients and febrile controls. On the contrary, acute-phase KS patients showed a significantly lower mean IL-18 value (398 ± 206 pg/ml) than that of febrile controls (584 ± 307 pg/ml) (p = 0.006). Subacute-phase KS patients showed a significantly elevated level of IL-18 (517 ± 276 pg/ml) compared to acute-phase patients (p = 0.0008). The IL-18 values in the subacute-phase patients showed a significant positive correlation with the duration of fever (r = 0.427, p = 0.0055) and also with the presence of coronary artery abnormalities (r = 0.332, p = 0.0340). The incidence of elevated IL-18 values in the subacute-phase patients was significantly higher than that in the afebrile controls (p = 0.048). Conclusions: Patients with KS showed normal IL-18 values in the acute phase and elevated values in the subacute phase. IL-18 pathways were activated in the subacute phase of KS, and subacute IL-18 values might be reflected in the severity of KS.

Keywords:
Kawasaki syndrome, Interleukin-18, Th1, Th2
1.
Japan Kawasaki Disease Research Committee: Diagnostic Guidelines of Kawasaki Disease, ed 5. Tokyo, Japan Kawasaki Disease Research Committee, 2002.
2.
Rowley AH, Shulman ST: Kawasaki disease; in Behrman RE, Kliegman RM, Jenson HB: Textbook of Pediatrics, ed 16. Philadelphia, WB Saunders, 2000, pp 725–727.
3.
Suzuki H, Noda E, Miyawaki M, Takeuchi T, Uemura S, Koike M: Serum levels of neutrophil activation cytokines in Kawasaki disease. Pediatr Int 2001;43:115–119.
4.
Leung DY, Siegel RL, Grady S, Krensky A, Meade R, Reinherz EL, Geha RS: Immunoregulatory abnormalities in mucocutaneous lymph node syndrome. Clin Immunol Immunopathol 1982;23:100–112.
5.
Furukawa S, Matsubara T, Jujho K, Yone K, Sugawara T, Sasaki K, Kato H, Yabuta K: Peripheral blood monocyte/macrophages and serum tumor necrosis factor in Kawasaki disease. Clin Immunol Immunopathol 1988;48:247–251.
6.
Furukawa S, Matsubara T, Motohashi T, Nakachi S, Sasai K, Yabuta K: Expression of Fc epsilon R2/CD23 on peripheral blood macrophages/monocytes in Kawasaki disease. Clin Immunol Immunopathol 1990;56:280–286.
7.
Rowley AH, Shulman ST, Preble OT, Poiesz BJ, Ehrlich GD, Sullivan JR: Serum interferon concentrations and retroviral serology in Kawasaki syndrome. Pediatr Infect Dis J 1988;7:663–666.
8.
Matsubara T, Furukawa S, Yabuta K: Serum levels of tumor necrosis factor, interleukin 2 receptor, and interferon-γ in Kawasaki disease involved coronary-artery lesions. Clin Immunol Immunopathol 1990;56:29–36.
9.
Hahn Y, Kim Y, Jo S, Han H: Reduced frequencies of peripheral interferon-γ-producing CD4+ and CD4– cells during acute Kawasaki disease. Int Arch Allergy Immunol 2000;122:293–298.
10.
Maury CP, Salo E, Pelkonen P: Circulating interleukin-1 beta in patients with Kawasaki disease. N Engl J Med 1988;319:1670–1671.
11.
Lin CY, Lin CC, Hwang B, Chiang BN: Cytokines predict coronary aneurysm formation in Kawasaki disease patients. Eur J Pediatr 1993;152:309–312.
12.
Hirao J, Hibi S, Andoh T, Ichimura T: High levels of circulating interleukin-4 and interleukin-10 in Kawasaki disease. Int Arch Allergy Immunol 1997;112:152–156.
13.
Okamura H, Nagata K, Komatsu T, Tanimoto T, Nukata Y, Tanabe F, Akita K, Torigoe K, Okura T, Fukuda S, Kurimoto M: A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock. Infect Immun 1995;63:3966–3972.
14.
Okamura H, Tsutsui H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K, Akita K, Namba M, Tanabe F, Konishi K, Fukuda S, Kurimoto M: Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995;378:88–91.
15.
Pizarro TT, Michie MH, Bentz M, Woraratanadharm J, Smith MF Jr, Foley E, Moskaluk CA, Bickston SJ, Cominelli F: IL-18, a novel immunoregulatory cytokine, is up-regulated in Crohn’s disease: Expression and localization in intestinal mucosal cells. J Immunol 1999;162:6829–6835.
16.
Kawashima M, Yamamura M, Taniai M, Yamauchi H, Tanimoto T, Kurimoto M, Miyawaki S, Amano T, Takeuchi T, Makino H: Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients with adult-onset Still’s disease. Arthritis Rheum 2001;44:550–560.
17.
Maeno N, Takei S, Nomura Y, Imanaka H, Hokonohara M, Miyata K: Highly elevated serum levels of interleukin-18 in systemic juvenile idiopathic arthritis but not in other juvenile idiopathic arthritis subtypes or in Kawasaki disease. Arthritis Rheum 2002;46:2539–2541.
18.
Sawaji Y, Haneda N, Yamaguchi S, Kajino Y, Kishida K, Seto S, Konishi N, Waki K, Baba K, Arisawa K, Kamiya T, Mori C: Coronary risk factors in acute Kawasaki disease: Correlation of serum immunoglobulin levels with coronary complications. Acta Paediatr Jpn 1998;40:218–225.
19.
Nomura Y, Masuda K, Yoshinaga M, Sameshima K, Miyata K: Patients diagnosed with Kawasaki disease before the fifth day of illness have a higher risk of coronary artery aneurysm. Pediatr Int 2002;44:353–357.
20.
Mosmann TR, Sad S: The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996;17:138–146.
© 2004 S. Karger AG, Basel
2004
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.