Skip to main content
Erschienen in: Zeitschrift für Rheumatologie 2/2018

19.09.2016 | Originalien

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

verfasst von: 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, M.D., J. Wang, M.D.

Erschienen in: Zeitschrift für Rheumatologie | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

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.
Literatur
2.
Zurück zum Zitat Naraghi K, van Laar JM (2013) Update on stem cell transplantation for systemic sclerosis: recent trial results. Curr Rheumatol Rep 15(5):326CrossRefPubMed Naraghi K, van Laar JM (2013) Update on stem cell transplantation for systemic sclerosis: recent trial results. Curr Rheumatol Rep 15(5):326CrossRefPubMed
3.
Zurück zum Zitat Aden N, Nuttall A, Shiwen X, de Winter P, Leask A, Black CM et al (2010) Epithelial cells promote fibroblast activation via IL-1alpha in systemic sclerosis. J Invest Dermatol 130(9):2191–2200CrossRefPubMed Aden N, Nuttall A, Shiwen X, de Winter P, Leask A, Black CM et al (2010) Epithelial cells promote fibroblast activation via IL-1alpha in systemic sclerosis. J Invest Dermatol 130(9):2191–2200CrossRefPubMed
4.
Zurück zum Zitat Hussein MR, Hassan HI, Hofny ER, Elkholy M, Fatehy NA, Abd Elmoniem AE et al (2005) Alterations of mononuclear inflammatory cells, CD4/CD8+ T cells, interleukin 1beta, and tumour necrosis factor alpha in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis. J Clin Pathol 58(2):178–184CrossRefPubMedPubMedCentral Hussein MR, Hassan HI, Hofny ER, Elkholy M, Fatehy NA, Abd Elmoniem AE et al (2005) Alterations of mononuclear inflammatory cells, CD4/CD8+ T cells, interleukin 1beta, and tumour necrosis factor alpha in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis. J Clin Pathol 58(2):178–184CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Kawaguchi Y, Hara M, Wright TM (1999) Endogenous IL-1alpha from systemic sclerosis fibroblasts induces IL-6 and PDGF-A. J Clin Invest 103(9):1253–1260CrossRefPubMedPubMedCentral Kawaguchi Y, Hara M, Wright TM (1999) Endogenous IL-1alpha from systemic sclerosis fibroblasts induces IL-6 and PDGF-A. J Clin Invest 103(9):1253–1260CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Kawaguchi Y, McCarthy SA, Watkins SC, Wright TM (2004) Autocrine activation by interleukin 1alpha induces the fibrogenic phenotype of systemic sclerosis fibroblasts. J Rheumatol 31(10):1946–1954PubMed Kawaguchi Y, McCarthy SA, Watkins SC, Wright TM (2004) Autocrine activation by interleukin 1alpha induces the fibrogenic phenotype of systemic sclerosis fibroblasts. J Rheumatol 31(10):1946–1954PubMed
8.
Zurück zum Zitat Hu B, Wang S, Zhang Y, Feghali CA, Dingman JR, Wright TM (2003) A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression. Proc Natl Acad Sci USA 100(17):10008–10013CrossRefPubMedPubMedCentral Hu B, Wang S, Zhang Y, Feghali CA, Dingman JR, Wright TM (2003) A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression. Proc Natl Acad Sci USA 100(17):10008–10013CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Kawaguchi Y, Harigai M, Suzuki K, Hara M, Kobayashi K, Ishizuka T et al (1993) Interleukin 1 receptor on fibroblasts from systemic sclerosis patients induces excessive functional responses to interleukin 1 beta. Biochem Biophys Res Commun 190(1):154–161CrossRefPubMed Kawaguchi Y, Harigai M, Suzuki K, Hara M, Kobayashi K, Ishizuka T et al (1993) Interleukin 1 receptor on fibroblasts from systemic sclerosis patients induces excessive functional responses to interleukin 1 beta. Biochem Biophys Res Commun 190(1):154–161CrossRefPubMed
10.
Zurück zum Zitat Lim MA, Lee J, Park JS, Jhun JY, Moon YM, Cho ML et al (2014) Increased Th17 differentiation in aged mice is significantly associated with high IL-1beta level and low IL-2 expression. Exp Gerontol 49:55–62CrossRefPubMed Lim MA, Lee J, Park JS, Jhun JY, Moon YM, Cho ML et al (2014) Increased Th17 differentiation in aged mice is significantly associated with high IL-1beta level and low IL-2 expression. Exp Gerontol 49:55–62CrossRefPubMed
11.
Zurück zum Zitat Vettori S, Cuomo G, Iudici M, D’Abrosca V, Giacco V, Barra G et al (2014) Early systemic sclerosis: serum profiling of factors involved in endothelial, T‑cell, and fibroblast interplay is marked by elevated interleukin-33 levels. J Clin Immunol 34(6):663–668CrossRefPubMed Vettori S, Cuomo G, Iudici M, D’Abrosca V, Giacco V, Barra G et al (2014) Early systemic sclerosis: serum profiling of factors involved in endothelial, T‑cell, and fibroblast interplay is marked by elevated interleukin-33 levels. J Clin Immunol 34(6):663–668CrossRefPubMed
12.
Zurück zum Zitat Komai-Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY (2007) IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol 37(10):2779–2786CrossRefPubMed Komai-Koma M, Xu D, Li Y, McKenzie AN, McInnes IB, Liew FY (2007) IL-33 is a chemoattractant for human Th2 cells. Eur J Immunol 37(10):2779–2786CrossRefPubMed
13.
Zurück zum Zitat Yanaba K, Yoshizaki A, Asano Y, Kadono T, Sato S (2011) Serum IL-33 levels are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. Clin Rheumatol 30(6):825–830CrossRefPubMed Yanaba K, Yoshizaki A, Asano Y, Kadono T, Sato S (2011) Serum IL-33 levels are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. Clin Rheumatol 30(6):825–830CrossRefPubMed
14.
Zurück zum Zitat Manetti M, Guiducci S, Ceccarelli C, Romano E, Bellando-Randone S, Conforti ML et al (2011) Increased circulating levels of interleukin 33 in systemic sclerosis correlate with early disease stage and microvascular involvement. Ann Rheum Dis 70(10):1876–1878CrossRefPubMed Manetti M, Guiducci S, Ceccarelli C, Romano E, Bellando-Randone S, Conforti ML et al (2011) Increased circulating levels of interleukin 33 in systemic sclerosis correlate with early disease stage and microvascular involvement. Ann Rheum Dis 70(10):1876–1878CrossRefPubMed
15.
Zurück zum Zitat Terras S, Opitz E, Moritz RK, Hoxtermann S, Gambichler T, Kreuter A (2013) Increased serum IL-33 levels may indicate vascular involvement in systemic sclerosis. Ann Rheum Dis 72(1):144–145CrossRefPubMed Terras S, Opitz E, Moritz RK, Hoxtermann S, Gambichler T, Kreuter A (2013) Increased serum IL-33 levels may indicate vascular involvement in systemic sclerosis. Ann Rheum Dis 72(1):144–145CrossRefPubMed
16.
Zurück zum Zitat Xu WD, Pan HF, Ye DQ (2013) Association of interleukin-18 and systemic lupus erythematosus. Rheumatol Int 33(12):3055–3057CrossRefPubMed Xu WD, Pan HF, Ye DQ (2013) Association of interleukin-18 and systemic lupus erythematosus. Rheumatol Int 33(12):3055–3057CrossRefPubMed
17.
Zurück zum Zitat Volin MV, Koch AE (2011) Interleukin-18: a mediator of inflammation and angiogenesis in rheumatoid arthritis. J Interferon Cytokine Res 31(10):745–751CrossRefPubMed Volin MV, Koch AE (2011) Interleukin-18: a mediator of inflammation and angiogenesis in rheumatoid arthritis. J Interferon Cytokine Res 31(10):745–751CrossRefPubMed
18.
Zurück zum Zitat Artlett CM, Sassi-Gaha S, Rieger JL, Boesteanu AC, Feghali-Bostwick CA, Katsikis PD (2011) The inflammasome activating caspase 1 mediates fibrosis and myofibroblast differentiation in systemic sclerosis. Arthritis Rheum 63(11):3563–3574CrossRefPubMed Artlett CM, Sassi-Gaha S, Rieger JL, Boesteanu AC, Feghali-Bostwick CA, Katsikis PD (2011) The inflammasome activating caspase 1 mediates fibrosis and myofibroblast differentiation in systemic sclerosis. Arthritis Rheum 63(11):3563–3574CrossRefPubMed
20.
Zurück zum Zitat Kim HJ, Song SB, Choi JM, Kim KM, Cho BK, Cho DH et al (2010) IL-18 downregulates collagen production in human dermal fibroblasts via the ERK pathway. J Invest Dermatol 130(3):706–715CrossRefPubMed Kim HJ, Song SB, Choi JM, Kim KM, Cho BK, Cho DH et al (2010) IL-18 downregulates collagen production in human dermal fibroblasts via the ERK pathway. J Invest Dermatol 130(3):706–715CrossRefPubMed
21.
Zurück zum Zitat Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23(5):581–590CrossRef Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee (1980) Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 23(5):581–590CrossRef
22.
Zurück zum Zitat Slagter SN, van Vliet-Ostaptchouk JV, Vonk JM, Boezen HM, Dullaart RP, Kobold AC et al (2014) Combined effects of smoking and alcohol on metabolic syndrome: the LifeLines cohort study. PLOS ONE 9(4):e96406CrossRefPubMedPubMedCentral Slagter SN, van Vliet-Ostaptchouk JV, Vonk JM, Boezen HM, Dullaart RP, Kobold AC et al (2014) Combined effects of smoking and alcohol on metabolic syndrome: the LifeLines cohort study. PLOS ONE 9(4):e96406CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Zhang XLJ, Wang SH (2010) The effect of long-term alcohol intake on circadian rhythm of ambulatory blood pressure in males with hypertension. Chin J Hypertens 18:5CrossRef Zhang XLJ, Wang SH (2010) The effect of long-term alcohol intake on circadian rhythm of ambulatory blood pressure in males with hypertension. Chin J Hypertens 18:5CrossRef
24.
Zurück zum Zitat Huang J, Li M, Tian Z, Hsieh E, Wang Q, Liu Y et al (2014) Clinical and laboratory characteristics of systemic sclerosis patients with pulmonary arterial hypertension in China. Clin Exp Rheumatol 32(6 Suppl 86):115–121 Huang J, Li M, Tian Z, Hsieh E, Wang Q, Liu Y et al (2014) Clinical and laboratory characteristics of systemic sclerosis patients with pulmonary arterial hypertension in China. Clin Exp Rheumatol 32(6 Suppl 86):115–121
25.
Zurück zum Zitat Needleman BW, Wigley FM, Stair RW (1992) Interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha, and interferon-gamma levels in sera from patients with scleroderma. Arthritis Rheum 35(1):67–72CrossRefPubMed Needleman BW, Wigley FM, Stair RW (1992) Interleukin-1, interleukin-2, interleukin-4, interleukin-6, tumor necrosis factor alpha, and interferon-gamma levels in sera from patients with scleroderma. Arthritis Rheum 35(1):67–72CrossRefPubMed
26.
Zurück zum Zitat Maekawa T, Jinnin M, Ohtsuki M, Ihn H (2013) Serum levels of interleukin-1alpha in patients with systemic sclerosis. J Dermatol 40(2):98–101CrossRefPubMed Maekawa T, Jinnin M, Ohtsuki M, Ihn H (2013) Serum levels of interleukin-1alpha in patients with systemic sclerosis. J Dermatol 40(2):98–101CrossRefPubMed
27.
Zurück zum Zitat Umehara H, Kumagai S, Murakami M, Suginoshita T, Tanaka K, Hashida S et al (1990) Enhanced production of interleukin-1 and tumor necrosis factor alpha by cultured peripheral blood monocytes from patients with scleroderma. Arthritis Rheum 33(6):893–897CrossRefPubMed Umehara H, Kumagai S, Murakami M, Suginoshita T, Tanaka K, Hashida S et al (1990) Enhanced production of interleukin-1 and tumor necrosis factor alpha by cultured peripheral blood monocytes from patients with scleroderma. Arthritis Rheum 33(6):893–897CrossRefPubMed
28.
Zurück zum Zitat Andersen GN, Nilsson K, Nagaeva O, Rantapaa-Dahlqvist S, Sandstrom T, Mincheva-Nilsson L (2011) Cytokine mRNA profile of alveolar T lymphocytes and macrophages in patients with systemic sclerosis suggests a local Tr1 response. Scand J Immunol 74(3):272–281CrossRefPubMed Andersen GN, Nilsson K, Nagaeva O, Rantapaa-Dahlqvist S, Sandstrom T, Mincheva-Nilsson L (2011) Cytokine mRNA profile of alveolar T lymphocytes and macrophages in patients with systemic sclerosis suggests a local Tr1 response. Scand J Immunol 74(3):272–281CrossRefPubMed
29.
Zurück zum Zitat Astrakhantseva IV, Efimov GA, Drutskaya MS, Kruglov AA, Nedospasov SA (2014) Modern anti-cytokine therapy of autoimmune diseases. Biochemistry Mosc 79(12):1308–1321CrossRefPubMed Astrakhantseva IV, Efimov GA, Drutskaya MS, Kruglov AA, Nedospasov SA (2014) Modern anti-cytokine therapy of autoimmune diseases. Biochemistry Mosc 79(12):1308–1321CrossRefPubMed
30.
Zurück zum Zitat Sturner KH, Verse N, Yousef S, Martin R, Sospedra M (2014) Boswellic acids reduce Th17 differentiation via blockade of IL-1beta-mediated IRAK1 signaling. Eur J Immunol 44(4):1200–1212CrossRefPubMed Sturner KH, Verse N, Yousef S, Martin R, Sospedra M (2014) Boswellic acids reduce Th17 differentiation via blockade of IL-1beta-mediated IRAK1 signaling. Eur J Immunol 44(4):1200–1212CrossRefPubMed
31.
Zurück zum Zitat Mosaad YM, Metwally SS, Auf FA, AbdEL-Samee ER, el-Deek B, Limon NI et al (2003) Proinflammatory cytokines (IL-12 and IL-18) in immune rheumatic diseases: relation with disease activity and autoantibodies production. Egypt J Immunol 10(2):19–26PubMed Mosaad YM, Metwally SS, Auf FA, AbdEL-Samee ER, el-Deek B, Limon NI et al (2003) Proinflammatory cytokines (IL-12 and IL-18) in immune rheumatic diseases: relation with disease activity and autoantibodies production. Egypt J Immunol 10(2):19–26PubMed
32.
Zurück zum Zitat Pan HF, Wang J, Leng RX, Li XP, Ye DQ (2011) Interleukin-18: friend or foe for systemic sclerosis? J Invest Dermatol 131(12):2495–2497CrossRefPubMed Pan HF, Wang J, Leng RX, Li XP, Ye DQ (2011) Interleukin-18: friend or foe for systemic sclerosis? J Invest Dermatol 131(12):2495–2497CrossRefPubMed
33.
Zurück zum Zitat Sedimbi SK, Hagglof T, Karlsson MC (2013) IL-18 in inflammatory and autoimmune disease. Cell Mol Life Sci 70(24):4795–4808CrossRefPubMed Sedimbi SK, Hagglof T, Karlsson MC (2013) IL-18 in inflammatory and autoimmune disease. Cell Mol Life Sci 70(24):4795–4808CrossRefPubMed
34.
Zurück zum Zitat Nakamura K, Asano Y, Taniguchi T, Minatsuki S, Inaba T, Maki H et al (2016) Serum levels of interleukin-18-binding protein isoform a: Clinical association with inflammation and pulmonary hypertension in systemic sclerosis. J Dermatol. doi:10.1111/1346-8138.13252 Nakamura K, Asano Y, Taniguchi T, Minatsuki S, Inaba T, Maki H et al (2016) Serum levels of interleukin-18-binding protein isoform a: Clinical association with inflammation and pulmonary hypertension in systemic sclerosis. J Dermatol. doi:10.​1111/​1346-8138.​13252
35.
Zurück zum Zitat Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK et al (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2‑associated cytokines. Immunity 23(5):479–490CrossRefPubMed Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK et al (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2‑associated cytokines. Immunity 23(5):479–490CrossRefPubMed
36.
Zurück zum Zitat Koca SS, Pehlivan Y, Kara M, Alibaz-Oner F, Oztuzcu S, Yilmaz N et al (2016) The IL-33 gene is related to increased susceptibility to systemic sclerosis. Rheumatol Int 36(4):579–584CrossRefPubMed Koca SS, Pehlivan Y, Kara M, Alibaz-Oner F, Oztuzcu S, Yilmaz N et al (2016) The IL-33 gene is related to increased susceptibility to systemic sclerosis. Rheumatol Int 36(4):579–584CrossRefPubMed
37.
Zurück zum Zitat Rider P, Carmi Y, Voronov E, Apte RN (2013) Interleukin-1alpha. Semin Immunol 25(6):430–438CrossRefPubMed Rider P, Carmi Y, Voronov E, Apte RN (2013) Interleukin-1alpha. Semin Immunol 25(6):430–438CrossRefPubMed
Metadaten
Titel
Elevated serum levels of interleukin-1β and interleukin-33 in patients with systemic sclerosis in Chinese population
verfasst von
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, M.D.
J. Wang, M.D.
Publikationsdatum
19.09.2016
Verlag
Springer Medizin
Erschienen in
Zeitschrift für Rheumatologie / Ausgabe 2/2018
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI
https://doi.org/10.1007/s00393-016-0202-3

Weitere Artikel der Ausgabe 2/2018

Zeitschrift für Rheumatologie 2/2018 Zur Ausgabe

Update Rheumatologie

Spondyloarthritiden II

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.