Relationship between interleukin-6 and cardiac involvement in systemic sclerosis

Jurišić, Zrinka; Martinović-Kaliterna, Dušanka; Marasović-Krstulović, Daniela; Perković, Dijana; Tandara, Leida; Salamunić, Ilza; Carević, Vedran

doi:10.1093/rheumatology/ket131

Cited by 26 publications

(18 citation statements)

References 16 publications

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“…Recently, Jurisic et al . reported that IL-6 levels are increased in patients with SSc and correlate with LV diastolic dysfunction [36]. More studies are needed investigating the relationship of other biomarkers with diastolic dysfunction in patients with SSc.…”

Section: Discussionmentioning

confidence: 99%

Heart diastolic dysfunction in patients with systemic sclerosis

Ciurzyński¹,

Bienias²,

Irzyk³

et al. 2014

aoms

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IntroductionThere are limited data on left (LV) and right ventricular (RV) diastolic function in systemic sclerosis (SSc) patients especially in relation to biomarkers of matrix remodeling. The aim of the study was to analyze LV and RV myocardial diastolic function in SSc patients at baseline and after at least 1 year of follow-up and its relation to serum tissue inhibitors of metalloproteinase 1 (TIMP-1) level.Material and methodsWe prospectively studied 111 SSc patients (101 female, 10 male, age 54.2 ±13.8 years) and 21 age-matched controls (18 female, 3 male, age 49.3 ±10.5 years). After at least 1 year of observation (3.0 ±1.1 years) we reevaluated 69 of the SSc patients. Transthoracic echocardiography (Philips, iE33) for assessment of LV and RV diastolic function was performed and TIMP-1 serum level was measured.ResultsImpaired LV relaxation was observed in 38 (34%) SSc patients and in 1 (5%) of the controls (p < 0.001). The mean E/A ratio was lower in patients with SSc than in controls (p = 0.002) and significantly decreased after the follow-up period (p = 0.02). Impaired RV relaxation was detected in 25 (22.5%) SSc patients and in 1 (5%) control subject (p < 0.001) but did not deteriorate after follow-up. Mean serum level of TIMP-1 was significantly elevated in the follow-up group compared to baseline examination (p = 0.0001). Serum TIMP-1 level correlated positively with E/E’, both septal and lateral (r = 0.4, p = 0.002 and r = 0.32, p = 0.01).ConclusionsThe LV and RV relaxation is impaired in SSc patients. Moreover, left ventricular diastolic function deteriorated after the follow-up period. The TIMP-1 serum levels correlate with echocardiographic parameters, providing a potent link for LV diastolic function and matrix remodeling in patients with SSc.

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Section: Discussionmentioning

confidence: 99%

Heart diastolic dysfunction in patients with systemic sclerosis

Ciurzyński¹,

Bienias²,

Irzyk³

et al. 2014

aoms

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“…Plasma IL-6 level was found to be higher in ATA-positive and anti-RNAP III-positive patients but not in ACA-positive SSc patients [ 60 ]. In one study, serum IL-6 was shown to correlate with disease activity [ 61 ], although this was not found by others [ 62 ]. In a genetic association study, IL-6 polymorphism in SSc patients was shown to be associated with disease activity and HAQ-DI, unfortunately circulating IL-6 was not measured [ 63 ].…”

Section: Biomarkers For Disease Activitymentioning

confidence: 92%

Update on biomarkers in systemic sclerosis: tools for diagnosis and treatment

2015

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Systemic sclerosis (SSc) is a complex autoimmune disease in which immune activation, vasculopathy, and extensive fibrosis of the skin and internal organs are among the principal features. SSc is a heterogeneous disease with varying manifestations and clinical outcomes. Currently, patients’ clinical evaluation often relies on subjective measures, non-quantitative methods, or requires invasive procedures as markers able to predict disease trajectory or response to therapy are lacking. Therefore, current research is focusing on the discovery of useful biomarkers reflecting ongoing inflammatory or fibrotic activity in the skin and internal organs, as well as being predictive of future disease course. Recently, remarkable progress has been made towards a better understanding of numerous mechanisms involved in the pathogenesis of SSc. This has opened new possibilities for the development of novel biomarkers and therapy. However, current proposed biomarkers that could reliably describe various aspects of SSc still require further investigation. This review will summarize studies describing the commonly used and validated biomarkers, the newly emerging and promising SSc biomarkers identified to date, and consideration of future directions in this field.

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“…The complex of IL-6-soluble IL-6R,andIL-6-anti-IL-6autoantibodycanbindtogp130and induce signal transduction in SSc (68,69). Significant correlationshavebeenobservedbetweenserumlevelsofIL-6 andtheseverityofskinthickening(70),diseaseprogression ininterstitiallungdisease(63),andcardiacinvolvement (64,65);thesecomplicationsofSScarecharacterizedbytissuefibrosis.InadditiontoelevatedcirculatingIL-6levels,cultured fibroblastsfromSScpatientswerefoundtoexpressstrikingly high levels of IL-6 at both the transcriptional and the proteinlevels (71)(72)(73)(74).InhibitionofIL-6signaltransductionusing ananti-IL-6antibodyattenuatedcollagenproductionincul-turedfibroblastsofSScpatients (14). Additionally,elevated secretion of IL-6 from peripheral monocytes was observed inpatientswithSSc-associatedinterstitiallungdisease(75).…”

Section: Elevation Of Il-6 In Sscmentioning

confidence: 99%

“…Insummary,highconcentrationsofIL-6arefoundinthe seraofSScpatients (10)(11)(12)(13)15,(63)(64)(65)andhavebeenshown tobehighlycorrelatedwiththeseverityoftissuefibrosis.In vitroexperimentsfurthersupporttheseobservations,demonstratinganincreasedsecretionofIL-6byculturedskinfi-broblasts,monocytes,andBlymphocytesfrompatientswith SSc (71)(72)(73)(74)(75)(76).Inparticular,theoverproductionofIL-6canlead to excessive collagen production by fibroblasts, which contributestotissuefibrosisinSSc (11,13,14) (Fig.2).…”

Section: Elevation Of Il-6 In Sscmentioning

confidence: 99%

Contribution of Interleukin-6 to the Pathogenesis of Systemic Sclerosis

Kawaguchi

2017

Journal of Scleroderma and Related Disorders

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Systemicsclerosis(SSc)isaconnectivetissuediseaseofunknownetiology,manifestinginpatientsastissuefibrosis,endothelialdysfunction,andinflammation.Thediseaseischaracterizedbyautoantibodies,ahallmarkof autoimmunity.Variouscytokinesandgrowthfactorsareelevatedinthesystemiccirculationandfibroticlesions ofpatientswithSSc.Inparticular,severalstudiesoverthepast2decadeshaveshownthatinterleukin-6(IL-6) appearstobeinvolvedinthepathogenesisofSSc.BasedontheassociationbetweenaberrantIL-6production andtissuefibrosisinpatientswithSSc,theanti-IL-6receptorantibody,tocilizumab,isbeinginvestigatedinclinical trials.ThisarticlereviewsthebiologicalfeaturesofIL-6andtheIL-6receptor;theroleofIL-6inthepathogenesis ofSSc;andthepotentialforIL-6inhibitiontobeusedinthetreatmentofpatientswithSSc.

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Relationship between interleukin-6 and cardiac involvement in systemic sclerosis

Abstract: IL-6 level is increased in patients with SSc and significantly correlates with LV diastolic dysfunction, NT-proBNP and EUSTAR score. These results support the role of IL-6 in the development of cardiac disease in SSc patients.

Cited by 26 publications

References 16 publications

Heart diastolic dysfunction in patients with systemic sclerosis

Heart diastolic dysfunction in patients with systemic sclerosis

Update on biomarkers in systemic sclerosis: tools for diagnosis and treatment

Contribution of Interleukin-6 to the Pathogenesis of Systemic Sclerosis

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