Clinical Rheumatology

, Volume 26, Issue 8, pp 1332–1334

Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis

  • Marija Jelušić
  • Ivan Krešimir Lukić
  • Lana Tambić-Bukovac
  • Klara Dubravčić
  • Ivan Malčić
  • Igor Rudan
  • Drago Batinić
Brief Report


The objective of this report is to explore the balance between serum and synovial fluid levels of interleukin (IL)-18 in children with juvenile idiopathic arthritis (JIA). Blood samples were obtained from 81 children with JIA and 18 control children. Synovial fluid samples were collected from 16 children with oligoarticular JIA. Concentrations of IL-18 were determined using commercial kit. Patients with systemic JIA had higher serum levels of IL-18 than patients with other forms of JIA or control children, both during the active (median, range: 6,240, 1,600–78,750 pg/ml) and inactive (1,615, 513–3,270 pg/ml) phase of disease [analysis of variance (ANOVA), P < 0.05). Levels of IL-18 in sera of children with oligoarticular JIA (255, 89–4,342 pg/ml) were similar to the respective synovial fluid levels (217, 89–1,245 pg/ml). Serum levels of IL-18 were proportional to the erythrocyte sedimentation rate and levels of C-reactive protein, but inversely proportional to the haemoglobin levels. IL-18 appears to be an important mediator of systemic JIA, while it seems of a lesser relevance in pathogenesis of other JIA forms. Therefore, inhibition of IL-18 might be a base for a successful biological therapy for systemic JIA.


Inflammation Interleukin-18 Juvenile idiopathic arthritis 


  1. 1.
    Sullivan KA (2005) Inflammation in juvenile idiopathic arthritis. Pediatr Clin N Am 52:335–357CrossRefGoogle Scholar
  2. 2.
    Mangge H, Vojinovic J, Schauenstein K (2002) Do chemokines spark autoimmunity in juvenile and adult rheumatic disease? Immunobiology 206:459–471PubMedCrossRefGoogle Scholar
  3. 3.
    Wilkinson N, Jackson G, Gardner-Medwin J (2003) Biologic therapies for juvenile arthritis. Arch Dis Child 88:186–191PubMedCrossRefGoogle Scholar
  4. 4.
    de Kleer IM, Wedderburn LR, Taams LS, Patel A, Varsani H, Klein M, de Jager W, Pugayung G, Giannoni F, Rijkers G, Albani S, Kuis W, Prakken B (2004) CD4+CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol 172:6435–6443PubMedGoogle Scholar
  5. 5.
    de Benedetti F, Martini A (2005) Targeting the interleukin 6 receptor: a new treatment for systemic juvenile idiopathic arthritis? Arthritis Rheum 52:687–693PubMedCrossRefGoogle Scholar
  6. 6.
    Gracie JA, Robertson SE, McInnes IB (2003) Interleukin-18. J Leukoc Biol 73:213–224PubMedCrossRefGoogle Scholar
  7. 7.
    Gracie JA (2004) Interleukin-18 as a potential target in inflammatory arthritis. Clin Exp Immunol 136:402–404PubMedCrossRefGoogle Scholar
  8. 8.
    Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, Maldonado-Cocco J, Suarez-Almazor M, Orozco-Alcala J, Prieur AM (1998) Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol 25:1991–1994PubMedGoogle Scholar
  9. 9.
    Wallace CA, Ruperto N, Giannini E, Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology International Trials Organisation, Pediatric Rheumatology Collaborative Study Group (2004) Preliminary criteria for clinical remission for selected categories of juvenile idiopathic arthritis. J Rheumatol 31:2290–2294PubMedGoogle Scholar
  10. 10.
    Kawashima M, Yamamura M, Taniai M, Yamauchi H, Tanimoto T, Kurimoto M, Miyawaki S, Amano T, Takeuchi T, Makino H (2001) Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients with adult-onset Still’s disease. Arthritis Rheum 44:550–560PubMedCrossRefGoogle Scholar
  11. 11.
    Maeno N, Takei S, Nomura Y, Imanaka H, Hokonohara M, Miyata K (2002) Highly elevated serum levels of interleukin-18 in systemic juvenile idiopathic arthritis but not in other juvenile idiopathic arthritis subtypes or in Kawasaki disease: comment on the article by Kawashima et al. Arthritis Rheum 46:2539–2541PubMedCrossRefGoogle Scholar
  12. 12.
    Liew FY, McInnes IB (2002) Role of interleukin 15 and interleukin 18 in inflammatory response. Ann Rheum Dis 61(Suppl 2):ii100–ii102PubMedGoogle Scholar
  13. 13.
    Scola MP, Thompson SD, Brunner HI, Tsoras MK, Witte D, van Dijk MA, Grom AA, Passo MH, Glass DN (2002) Interferon-y:interleukin 4 ratio and associated type 1 cytokine expression in juvenile rheumatoid arthritis synovial tissue. J Rheumatol 29:369–378PubMedGoogle Scholar

Copyright information

© Clinical Rheumatology 2006

Authors and Affiliations

  • Marija Jelušić
    • 1
  • Ivan Krešimir Lukić
    • 2
  • Lana Tambić-Bukovac
    • 1
  • Klara Dubravčić
    • 3
  • Ivan Malčić
    • 1
  • Igor Rudan
    • 4
  • Drago Batinić
    • 3
  1. 1.Division of Paediatric Rheumatology, Department of PaediatricsZagreb University Hospital CentreZagrebCroatia
  2. 2.Department of AnatomyZagreb University School of MedicineZagrebCroatia
  3. 3.Division of Immunology, Department of Clinical Laboratory Diagnostics, Zagreb University Hospital CentreZagreb University School of MedicineZagrebCroatia
  4. 4.Department of Medical Statistics, Epidemiology, and Medical Informatics, Andrija Štampar School of Public HealthZagreb University School of MedicineZagrebCroatia

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