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

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 re...

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Autores principales: Dragoljevic, Dragana, Lee, Man Kit Sam, Louis, Cynthia, Shihata, Waled, Kraakman, Michael J, Hansen, Jacinta, Masters, Seth L, Hanaoka, Beatriz Y, Nagareddy, Prabhakara R, Lancaster, Graeme I, Wicks, Ian P, Murphy, Andrew J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652637/
https://www.ncbi.nlm.nih.gov/pubmed/33204425
http://dx.doi.org/10.1002/cti2.1206
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author Dragoljevic, Dragana
Lee, Man Kit Sam
Louis, Cynthia
Shihata, Waled
Kraakman, Michael J
Hansen, Jacinta
Masters, Seth L
Hanaoka, Beatriz Y
Nagareddy, Prabhakara R
Lancaster, Graeme I
Wicks, Ian P
Murphy, Andrew J
author_facet Dragoljevic, Dragana
Lee, Man Kit Sam
Louis, Cynthia
Shihata, Waled
Kraakman, Michael J
Hansen, Jacinta
Masters, Seth L
Hanaoka, Beatriz Y
Nagareddy, Prabhakara R
Lancaster, Graeme I
Wicks, Ian P
Murphy, Andrew J
author_sort Dragoljevic, Dragana
collection PubMed
description 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.
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spelling pubmed-76526372020-11-16 Inhibition of interleukin‐1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis Dragoljevic, Dragana Lee, Man Kit Sam Louis, Cynthia Shihata, Waled Kraakman, Michael J Hansen, Jacinta Masters, Seth L Hanaoka, Beatriz Y Nagareddy, Prabhakara R Lancaster, Graeme I Wicks, Ian P Murphy, Andrew J Clin Transl Immunology Short Communication 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. John Wiley and Sons Inc. 2020-11-09 /pmc/articles/PMC7652637/ /pubmed/33204425 http://dx.doi.org/10.1002/cti2.1206 Text en © 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Dragoljevic, Dragana
Lee, Man Kit Sam
Louis, Cynthia
Shihata, Waled
Kraakman, Michael J
Hansen, Jacinta
Masters, Seth L
Hanaoka, Beatriz Y
Nagareddy, Prabhakara R
Lancaster, Graeme I
Wicks, Ian P
Murphy, Andrew J
Inhibition of interleukin‐1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis
title Inhibition of interleukin‐1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis
title_full Inhibition of interleukin‐1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis
title_fullStr Inhibition of interleukin‐1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis
title_full_unstemmed Inhibition of interleukin‐1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis
title_short Inhibition of interleukin‐1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis
title_sort inhibition of interleukin‐1β signalling promotes atherosclerotic lesion remodelling in mice with inflammatory arthritis
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652637/
https://www.ncbi.nlm.nih.gov/pubmed/33204425
http://dx.doi.org/10.1002/cti2.1206
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