IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization

Rishi Batra, Melissa K. Suh, Jeffrey S. Carson, Matthew A. Dale, Trevor M. Meisinger, Matthew Fitzgerald, Patrick J. Opperman, Jiangtao Luo, Iraklis I Pipinos, Wanfen Xiong, Bernard Timothy Baxter

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective-Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation. Approach and Results-IL-1β was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1β and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1β deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-α. Bone marrow-derived macrophages from IL-1β-/- and TNF-α-/- mice were polarized to an M1 phenotype. TNF-α deletion, but not IL-1β deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-α-/- macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1β-/- macrophages. Conclusions-Although IL-1β is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-α. The differential effects of IL-1β and TNF-α inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1β and TNF-α antibody therapies in management of inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)457-463
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Issue number2
DOIs
StatePublished - Feb 1 2018

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Abdominal Aortic Aneurysm
Interleukin-1
Tumor Necrosis Factor-alpha
Macrophages
Cytokines
Aneurysm
Interleukins
Disease Management
Matrix Metalloproteinases
Cell Culture Techniques
Smoking
Phenotype
Antibodies

Keywords

  • cytokines
  • interleukin-1
  • macrophages
  • phenotype
  • tumor necrosis factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization. / Batra, Rishi; Suh, Melissa K.; Carson, Jeffrey S.; Dale, Matthew A.; Meisinger, Trevor M.; Fitzgerald, Matthew; Opperman, Patrick J.; Luo, Jiangtao; Pipinos, Iraklis I; Xiong, Wanfen; Baxter, Bernard Timothy.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 38, No. 2, 01.02.2018, p. 457-463.

Research output: Contribution to journalArticle

Batra, Rishi ; Suh, Melissa K. ; Carson, Jeffrey S. ; Dale, Matthew A. ; Meisinger, Trevor M. ; Fitzgerald, Matthew ; Opperman, Patrick J. ; Luo, Jiangtao ; Pipinos, Iraklis I ; Xiong, Wanfen ; Baxter, Bernard Timothy. / IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2018 ; Vol. 38, No. 2. pp. 457-463.
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abstract = "Objective-Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation. Approach and Results-IL-1β was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1β and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1β deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-α. Bone marrow-derived macrophages from IL-1β-/- and TNF-α-/- mice were polarized to an M1 phenotype. TNF-α deletion, but not IL-1β deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-α-/- macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1β-/- macrophages. Conclusions-Although IL-1β is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-α. The differential effects of IL-1β and TNF-α inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1β and TNF-α antibody therapies in management of inflammatory diseases.",
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T1 - IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization

AU - Batra, Rishi

AU - Suh, Melissa K.

AU - Carson, Jeffrey S.

AU - Dale, Matthew A.

AU - Meisinger, Trevor M.

AU - Fitzgerald, Matthew

AU - Opperman, Patrick J.

AU - Luo, Jiangtao

AU - Pipinos, Iraklis I

AU - Xiong, Wanfen

AU - Baxter, Bernard Timothy

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Objective-Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation. Approach and Results-IL-1β was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1β and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1β deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-α. Bone marrow-derived macrophages from IL-1β-/- and TNF-α-/- mice were polarized to an M1 phenotype. TNF-α deletion, but not IL-1β deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-α-/- macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1β-/- macrophages. Conclusions-Although IL-1β is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-α. The differential effects of IL-1β and TNF-α inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1β and TNF-α antibody therapies in management of inflammatory diseases.

AB - Objective-Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation. Approach and Results-IL-1β was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1β and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1β deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-α. Bone marrow-derived macrophages from IL-1β-/- and TNF-α-/- mice were polarized to an M1 phenotype. TNF-α deletion, but not IL-1β deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-α-/- macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1β-/- macrophages. Conclusions-Although IL-1β is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-α. The differential effects of IL-1β and TNF-α inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1β and TNF-α antibody therapies in management of inflammatory diseases.

KW - cytokines

KW - interleukin-1

KW - macrophages

KW - phenotype

KW - tumor necrosis factor

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