Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis
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OBJECTIVES: To compare the pro-inflammatory cytokine profiles and the cytokine kinetics in patients with secondary macrophage activation syndrome (MAS) due to systemic-onset juvenile idiopathic arthritis (s-JIA) and in both active and inactive disease states of s-JIA (but no MAS), with those demonstrated in EBV-induced haemophagocytic lymphohistiocytosis (HLH) and Kawasaki disease (KD), and to investigate the significance of IL-18 in the pathogenesis of s-JIA. METHODS: Five patients with MAS complicating s-JIA (MAS/s-JIA), 10 with HLH due to EBV infection (EBV-HLH), 22 with KD and 28 healthy controls were analysed. Cytokine concentrations (IL-18, IL-6, neopterin and TNF-alpha receptor Types I and II) were quantified in serum by ELISA. Results were compared with clinical features of MAS/s-JIA, including ferritin concentrations. RESULTS: Serum IL-18 concentrations in MAS/s-JIA patients were significantly higher than those in EBV-HLH or KD patients (P < 0.05). Serum IL-6 concentrations in KD patients were significantly higher than those in EBV-HLH or MAS/s-JIA patients. Serum neopterin concentrations in EBV-HLH patients were significantly higher than those in MAS/s-JIA or KD patients. Serum IL-18 correlated positively with the following measurements of disease activity: CRP, ferritin, lactate dehydrogenase and other cytokines (P < 0.05). Serum concentrations of IL-18 in s-JIA patients remained elevated in the inactive phase of disease, whereas clinical parameters and other cytokines normalized. CONCLUSIONS: IL-18 may be an important mediator in s-JIA. Although serum Il-18 concentrations correlated with markers of the disease activity, IL-18 concentrations remained elevated even when other markers of disease activity normalized. Serum IL-18 concentration may be a promising indicator of the disease activity. The cytokine release pattern in MAS/HLH is different among patients with different aetiologies. Monitoring the cytokine profile, including IL-18, may be useful for differentiation of MAS/HLH and evaluation of disease activity in s-JIA.
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Interleukin-18 is a biomarker of severity in macrophage activation syndrome that correlates with hyperferritinemia, elevated aminotransferase levels, and disease flare.
“interleukin-18 is a biomarker of severity that correlates with hyperferritinemia, elevated aminotransferase levels, and disease flare.45”
From Cytokine storm (2020) · cites this paper as [45]
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- Authors
- Shimizu, M., Yokoyama, T., Yamada, K., Kaneda, H., Wada, H., Wada, T., Toma, T., Ohta, K., Kasahara, Y., & Yachie, A.
- Affiliations
- Kanazawa University (JP)
- Venue
- Rheumatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-05-14
- Volume
- 49
- Issue
- 9
- Pages
- 1645-1653
- ISSN
- 1462-0324 (ISSN-L)
- 1462-0332
- OpenAlex
- W2128975003
- Cited by
- 255
- References
- 32
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 18 · 2023: 9 · 2022: 22 · 2021: 22 · 2020: 19 · 2019: 30 · 2018: 14 · 2017: 17 · 2016: 14 · 2015: 19 · 2014: 18 · 2013: 10 · 2012: 12
- FWCI
- 6.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Lara D. Veeken (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Surgery › Kawasaki Disease and Coronary Complications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- macrophage activation syndrome, systemic juvenile idiopathic arthritis, IL-18, cytokine profile, hemophagocytic lymphohistiocytosis, Epstein-Barr virus infection, Kawasaki disease, interleukin-6, neopterin, TNF receptor, ferritin, disease activity markers, pathogenesis
- MeSH terms
- Adolescent, Arthritis, Juvenile, Child, Child, Preschool, Female, Humans, Infant, Male, Statistics as Topic, Time Factors, Biomarkers, Case-Control Studies, Disease Progression, Interleukin-18, Macrophage Activation Syndrome
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