Author + information
- Mingxian Chen, MD,
- Qiming Liu, MD and
- Shenghua Zhou, MD∗ ()
- ↵∗Department of Cardiology, The Second Xiangya Hospital of Central South University, No. 139 Middle Renmin Road, Furong District, Changsha City, Hunan Province 410011, China
Recently, we read with great interest a review by Libby et al. (1). In this review, they demonstrated that leukocytes act as prostaglandins in atherosclerosis and build up important neuroimmune networks. However, there are some concerns about how the sympathetic nervous system (SNS) interacts with the immune response in atherosclerosis.
The SNS exerts complex control over inflammation in atherosclerosis both on a systemic scale and at the regional level (Figure 1). SNS fibers innervate the primary and second lymphoid organs (bone marrow, thymus, spleen, lymph nodes) involved in immune modulation. The SNS contributes to the differentiation, maturation, recruitment, and regulation of immune cells via lymphoid organs. The SNS is also a modulator in thymus, spleen, and lymph node and can modulate the recognition, proliferation, and effector phases of the immune response. It influences immune cell migration and alters cytokine production (2,3).
What’s more, the SNS directly innervates the target lesion and plays a proinflammatory role in immune cells. First, norepinephrine released from sympathetic nerve endings binds to α- or β-adrenergic receptors expressed on immune cells (T cells, B cells, natural killer cells, and macrophages). This response gives rise to a cascade of events, including the production of proinflammatory cytokines and recruitment of leukocytes (4). Second, the SNS releases neuropeptide Y, which increases the adhesion of human leukocytes to endothelial cells. Third, the SNS might also exert an influence on vascular and lymphatic smooth muscle regulating the blood flow or lymph flow and thereby lymphocyte delivery (5).
Furthermore, peripherally secreted proinflammatory cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor-α, can signal to the brain via the circulation or through afferent fibers, which in turn leads to activation of the SNS (2). This might form a vicious circle between SNS activity and inflammatory disease (atherosclerosis).
Please note: This work was supported by grants from the National Natural Science Foundation of China (No. 81270257). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- American College of Cardiology Foundation
- Libby P.,
- Nahrendorf M.,
- Swirski F.K.
- Sundman E.,
- Olofsson P.S.