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

Dragoljevic, D; Lee, MKS; Louis, C; Shihata, W; Kraakman, MJ; Hansen, J; Masters, SL; Hanaoka, BY; Nagareddy, PR; Lancaster, GI; Wicks, IP; Murphy, AJ

Author(s): Dragoljevic, D; Lee, MKS; Louis, C; Shihata, W; Kraakman, MJ; Hansen, J; Masters, SL; Hanaoka, BY; Nagareddy, PR; Lancaster, GI; Wicks, IP; Murphy, AJ;
Details: Publication Year 2020,Volume 9,Issue #11,Page e1206
Journal Title: Clin Transl Immunology
Publication Type: Journal Article
Abstract: OBJECTIVES: 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. METHODS: 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. RESULTS: 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 splenic extramedullary myelopoiesis. CONCLUSION: We show that inhibiting IL-1 signalling in arthritic mice with pre-existing atherosclerosis promotes lesion remodelling to a more stable phenotype, that is less likely to rupture and cause ischemic events such as myocardial infarction. This suggests that IL-1R antagonism may suppress CVD complications in patients with RA. Furthermore, inhibiting IL-1β signalling in other patients with inflammatory diseases that also predispose to CVD may also benefit from anti-IL-1 therapy.
Publisher: Wiley
Keywords: atherosclerosis; inflammation; interleukin 1β; monocytes; rheumatoid arthritis
Research Division(s): Inflammation
PubMed ID: 33204425
Publisher's Version: https://doi.org/10.1002/cti2.1206
Open Access at Publisher's Site: https://doi.org/10.1002/cti2.1206
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-02-01 12:07:31

Last Modified: 2021-03-02 11:34:31