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The role of interleukin-6 trans-signalling on cardiovascular dysfunction in inflammatory arthritis.

Authors :
Davies, Ruth
Williams, Jessica
Sime, Katie
Jin, Hyun-Sun
Thompson, Charlotte
Jordan, Lauren
Lang, Derek
Halcox, Julian P
Ellins, Elizabeth
Jones, Gareth W
Jones, Simon A
Rose-John, Stefan
Williams, Anwen
Choy, Ernest
Source :
Rheumatology; Jun2021, Vol. 60 Issue 6, p2852-2861, 10p
Publication Year :
2021

Abstract

Objectives Cardiovascular (CV) mortality in RA patients is 50% higher than in the general population. There is increasing recognition that systemic inflammation is a major driver of this. IL-6 is implicated in cardiovascular disease (CVD) in the general population but its role in CVD in RA is undefined. Of the two modes of IL-6 signalling, trans-signalling is pro-inflammatory whereas classical signalling is linked with inflammation resolution. This study examines the role of IL-6 trans-signalling in CVD in a mouse model and patients with RA. Methods Myography determined the effect of IL-6 trans-signalling blockade, using sgp130Fc, on aortic constriction in murine collagen-induced arthritis. Serum CCL2 and sVCAM-1 as soluble biomarkers of sIL-6R trans-signalling were investigated in a human cross-sectional study. An observational longitudinal study investigated the association between these biomarkers and progression of subclinical atherosclerosis in early RA by measuring carotid intima-media thickness (CIMT). Results sgp130Fc reduced arthritis severity, serum CCL2 and sVCAM-1 and restored vascular function in collagen-induced arthritis (CIA). In established RA, sVCAM-1 correlated with the 28-joint DAS (DAS28) and CV risk. In early RA, baseline DAS28 was associated with CIMT change at 6 months. CIMT 'rapid progressors' at 12 months had higher baseline sVCAM-1, haemoglobin A1c, cholesterol:high-density lipoprotein cholesterol ratio and LDL cholesterol. Conclusions IL-6 trans-signalling plays a pivotal role in vascular dysfunction in CIA. In early RA, sVCAM-1 was associated with progression of subclinical atherosclerosis. Inflammation from RA onset in CVD-susceptible individuals may accelerate atherosclerosis. IL-6 trans-signalling blockade may be beneficial to RA patients and perhaps for atherosclerosis in the general population. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14620324
Volume :
60
Issue :
6
Database :
Complementary Index
Journal :
Rheumatology
Publication Type :
Academic Journal
Accession number :
151011144
Full Text :
https://doi.org/10.1093/rheumatology/keaa725