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An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
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An Adoptive Transfer Model of Rheumatoid Arthritis in Mice

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

Ruth Davies1, Jessica Williams1, Katie Sime1

  • 1CREATE Centre, Division of Infection and Immunity, , Cardiff, UK.

Rheumatology (Oxford, England)
|December 14, 2020
PubMed

Insights

Interleukin-6 (IL-6) trans-signalling drives vascular dysfunction in rheumatoid arthritis (RA). Blocking this pathway may improve cardiovascular health in RA patients and potentially the general population.

Area of Science:

  • Rheumatology
  • Cardiovascular Science
  • Immunology

Background:

  • Rheumatoid arthritis (RA) patients face a 50% higher cardiovascular (CV) mortality rate compared to the general population.
  • Systemic inflammation is increasingly recognized as a key contributor to cardiovascular disease (CVD) in RA.
  • The specific role of Interleukin-6 (IL-6) signalling, particularly trans-signalling, in RA-associated CVD remains undefined.

Purpose of the Study:

  • To investigate the role of IL-6 trans-signalling in the development of CVD in a mouse model of RA.
  • To examine the association between IL-6 trans-signalling biomarkers and subclinical atherosclerosis progression in human RA patients.
  • To evaluate the potential therapeutic benefit of blocking IL-6 trans-signalling in RA and CVD.

Main Methods:

  • Utilized myography to assess the impact of IL-6 trans-signalling blockade (sgp130Fc) on aortic constriction in murine collagen-induced arthritis (CIA).
  • Measured serum CCL2 and soluble VCAM-1 (sVCAM-1) as biomarkers for IL-6 trans-signalling in human RA cohorts (cross-sectional and longitudinal).
  • Employed carotid intima-media thickness (CIMT) to track subclinical atherosclerosis progression in early RA patients over 12 months.

Main Results:

  • IL-6 trans-signalling blockade with sgp130Fc reduced arthritis severity, lowered serum CCL2 and sVCAM-1, and improved vascular function in CIA mice.
  • In established RA, sVCAM-1 correlated with disease activity (DAS28) and cardiovascular risk.
  • In early RA, higher baseline sVCAM-1, HbA1c, and lipid ratios were associated with accelerated CIMT progression.

Conclusions:

  • IL-6 trans-signalling is a critical factor in vascular dysfunction observed in collagen-induced arthritis.
  • sVCAM-1 serves as a biomarker for subclinical atherosclerosis progression in early RA.
  • Targeting IL-6 trans-signalling may offer a promising therapeutic strategy for managing cardiovascular risk in RA and potentially in the broader population.
Abstract

Keywords:
RAcardiovascular diseasesexperimental arthritisinflammation

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