Inhibition of interleukin-1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis

Clinical & Translational Immunology
Dragana DragoljevicAndrew J Murphy

Abstract

Rheumatoid arthritis (RA), an inflammatory joint disorder, independently increases the risk of cardiovascular disease (CVD). IL-1β contributes to both RA and CVD. We hypothesised that inhibiting IL-1 signalling with the IL-1R antagonist, anakinra, would dampen inflammation and promote resolution of atherosclerosis in arthritic mice. Low-density lipoprotein receptor (Ldlr)-deficient mice were fed a Western-type diet for 14 weeks to develop atherosclerotic plaques. Mice were then switched to a chow diet, promoting lesion regression, and randomised to a control group or into groups where arthritis was induced by passive transfer of K/BxN arthritogenic serum. The arthritic mice were further randomised to vehicle or anakinra. Arthritis impaired atherosclerotic lesion regression when cholesterol was lowered. This was associated with a higher burden of plaque macrophages, likely due to monocytosis, driven by myelopoiesis in the bone marrow and spleen. Interestingly, delayed intervention with anakinra had no effect on arthritis in these mice. However, a significant improvement in atherosclerotic plaque remodelling to a more stable phenotype was observed. This was associated with fewer circulating monocytes, caused by a reduction in spl...Continue Reading

References

Aug 1, 1983·Arthritis and Rheumatism·D D WoodP L Cohen
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Feb 8, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Andrew J MurphyLaurent Yvan-Charvet
May 9, 2014·Cell Metabolism·Prabhakara R NagareddyAndrew J Murphy
Apr 1, 2015·Nature Reviews. Rheumatology·Sarah Skeoch, Ian N Bruce
Feb 13, 2016·European Heart Journal·Andrew J Murphy, Alan R Tall
Jun 29, 2016·Clinical & Translational Immunology·Michael J KraakmanAndrew J Murphy
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Aug 29, 2017·The New England Journal of Medicine·Paul M RidkerUNKNOWN CANTOS Trial Group
Jan 17, 2020·Circulation·Gopalkrishna SreejitPrabhakara R Nagareddy

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Citations

Mar 7, 2021·Expert Review of Clinical Immunology·George A KarpouzasSarah R Ormseth

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

Adobe Photoshop
FlowJo

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