Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation

Area of Science:

• Immunology
• Cardiovascular Biology
• Genetics

Background:

• Interleukin-6 (IL-6) is a key cytokine in inflammation and cardiovascular disease.
• Myeloid cells are significant producers of IL-6.

Purpose of the Study:

• To create a mouse model to investigate the role of myeloid cell-derived IL-6 in vascular disease.
• To understand the specific contributions of IL-6 from myeloid sources to vascular pathology.

Main Methods:

• Generation of LysM-IL-6 overexpressing (LysM-IL-6OE) mice.
• Assessment of vascular function, inflammation, and survival in these mice.
• Bone marrow transplantation experiments to determine the source of IL-6's effects.

Main Results:

• LysM-IL-6OE mice developed inflammatory colitis and impaired aortic relaxation.
• Increased reactive oxygen species (ROS) formation, vascular dysfunction, and fibrosis were observed.
• Myeloid cell accumulation in the aorta and elevated inflammatory markers were noted.
• Bone marrow-derived IL-6 was found to be dose-dependently responsible for vascular dysfunction and ROS.

Conclusions:

• Conditional IL-6 overexpression in myeloid cells leads to systemic and vascular inflammation.
• Endothelial dysfunction and vascular disease are driven by IL-6 from myeloid sources.
• Reducing myeloid cell-derived IL-6 ameliorates vascular dysfunction, confirming its critical role.