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Elevated serum levels of interleukin-1β and interleukin-33 in patients with systemic sclerosis in Chinese population

Erhöhte Interleukin-1β- und Interleukin-33-Serumwerte bei Patienten mit systemischer Sklerose in einer chinesischen Population

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Abstract

Purpose of the study

Systemic sclerosis (SSc) is a multisystem autoimmune disease. Although the pathogenesis of the disease remains incompletely understood, some cytokines or growth factors which regulate SSc induction may be involved in the injury of endothelial cells and the modulation of leukocyte function. We aimed to perform this case–control study to determine serum levels of interleukin (IL)-1α, IL-1β, IL-18 and IL-33 and their associations with clinical manifestations in SSc patients.

Materials and methods

There were 56 patients with SSc and 56 healthy individuals who were recruited from local hospital between 2012 and 2014. Serum IL-1α, IL-1β, IL-18 and IL-33 levels were measured with specific enzyme-linked immunosorbent assay kits.

Results

Univariate analysis revealed that serum IL-1β, IL-18 and IL-33 levels in SSc patients were significantly higher than that in healthy controls. After adjusting possible confounding factors (sex, age, smoking and drinking) by multivariable analyses, serum IL-1β levels (OR = 1.082; 95 % CI: 1.013–1.155) and serum IL-33 levels (OR = 1.100; 95 %CI: 1.022–1.185) were still related factors. There were interrelationships among the serum levels of IL-1α, IL-1β, IL-18 and IL-33 and these associations were not consistent in SSc patients and controls. No associations of serum IL-1α, IL-1β, IL-18 and IL-33 levels with clinical parameters were found.

Conclusion

IL-1β and IL-33 may contribute to the development of SSc. While there were no direct associations between these cytokines and disease manifestations, they still could be considered as serum markers of development of SSc. Further studies are required to validate this incipient data.

Zusammenfassung

Zweck der Studie

Die systemische Sklerose (SSc) ist eine multisystemische Autoimmunerkrankung. Obwohl die Pathogenese der Erkrankung nicht vollständig verstanden ist, könnten einige Zytokine oder Wachstumsfaktoren, welche die Induktion der SSc regulieren, an der Verletzung von Endothelzellen und der Modulation der Leukozytenfunktion beteiligt sein. Das Ziel dieser Fall-Kontroll-Studie war es, die Serumwerte von Interleukin(IL)-1α, IL-1β, IL-18 und IL-33 sowie deren Assoziation mit den Krankheitsbildern von SSc-Patienten zu bestimmen.

Material und Methoden

Es wurden 56 Patienten mit SSc und 56 gesunde Personen eingeschlossen, die zwischen 2012 und 2014 von einem lokalen Krankenhaus rekrutiert worden waren. Die IL-1α-, IL-1β-, IL-18- und IL-33-Serumwerte wurden mit speziellen ELISA-Kits („enzyme-linked immunosorbent assay“) gemessen.

Ergebnisse

Eine univariate Analyse zeigte, dass die IL-1β-, IL-18- und IL-33-Serumwerte bei SSc-Patienten signifikant höher waren als die der gesunden Kontrollpersonen. Auch nach Anpassung möglicher Confounding-Faktoren (Geschlecht, Alter, Rauchen und Trinken) mittels multivariabler Analysen stellten die IL-1β-Werte (OR = 1,082; 95 % CI 1,013–1,155) und die IL-33-Werte (OR = 1,100; 95 % CI 1,022–1,185) noch zusammenhängende Faktoren dar. Es bestanden Wechselbeziehungen zwischen den IL-1α-, IL-1β-, IL-18- und IL-33-Serumwerten, die jedoch bei den SSc-Patienten und den gesunden Kontrollpersonen inkonsistent waren. Assoziationen zwischen IL-1α-, IL-1β-, IL-18- und IL-33-Serumwerten und klinischen Parametern wurden nicht gefunden.

Schlussfolgerung

IL-1β und IL-33 könnten zu der Entwicklung einer SSc beitragen. Während es keine direkten Assoziationen zwischen diesen Zytokinen und den Krankheitsbildern gab, könnten sie dennoch als Serummarker für die Entwicklung einer SSc in Betracht gezogen werden. Um diese ersten Daten zu validieren, bedarf es weiterer Studien.

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Acknowledgements

This work was partly supported by grants from the National Natural Science Foundation of China (Code: 81271759), Anhui Provincial Laboratory of Population Health & Major Disease Screening and Diagnosis, the Natural Science Foundation of Anhui Province in 2013 (Code: 1308085MH169), the Key Project of the Education Department of Anhui Province Natural Science Research (Code: KJ2012A165) and College Students’ Innovative Training Program in Anhui Province (Code: AH201410366097).

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Meishan Road 81, 230032, Hefei, Anhui, China

    Y.-J. Zhang, Q. Zhang, G.-C. Wu, X.-L. Huang, Y. Duan, D.-Q. Ye M.D. & J. Wang M.D.

  2. Department of Rheumatology and Immunology, Anhui Medical University, Anhui Provincial Hospital, Hefei, China

    G.-J. Yang, J.-H. Tao & X.-P. Li

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  1. Y.-J. Zhang
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  2. Q. Zhang
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  9. D.-Q. Ye M.D.
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Correspondence to D.-Q. Ye M.D. or J. Wang M.D..

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Conflict of interest

Y.-J. Zhang, Q. Zhang, G.-J. Yang, J.-H. Tao, G.-C. Wu, X.-L. Huang, Y. Duan, X.-P. Li, D.-Q. Ye and J. Wang state that they have no competing interest.

This article does not contain any studies with human participants or animals performed by any of the authors.

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U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

Y.-J. Zhang and Q. Zhang contributed equally to this work and should be considered co-first authors.

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Zhang, YJ., Zhang, Q., Yang, GJ. et al. Elevated serum levels of interleukin-1β and interleukin-33 in patients with systemic sclerosis in Chinese population. Z Rheumatol 77, 151–159 (2018). https://doi.org/10.1007/s00393-016-0202-3

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