Splenic autonomic denervation increases inflammatory status but does not aggravate atherosclerotic lesion development

Abstract

The brain plays a prominent role in the regulation of inflammation. Immune cells are under control of the so-called cholinergic anti-inflammatory reflex, mainly acting via autonomic innervation of the spleen. Activation of this reflex inhibits the secretion of proinflammatory cytokines and may reduce the development of atherosclerosis. Therefore, the aim of this study was to evaluate the effects of selective parasympathetic (Px) and sympathetic (Sx) denervation of the spleen on inflammatory status and atherosclerotic lesion development. Female APOE*3-Leiden.CETP mice, a well-established model for human-like lipid metabolism and atherosclerosis, were fed a cholesterol-containing Western-type diet for 4 wk after which they were subdivided into three groups receiving either splenic Px, splenic Sx, or sham surgery. The mice were subsequently challenged with the same diet for an additional 15 wk. Selective Px increased leukocyte counts (i.e., dendritic cells, B cells, and T cells) in the spleen and increased gene expression of proinflammatory cytokines in the liver and peritoneal leukocytes compared with Sx and sham surgery. Both Px and Sx increased circulating proinflammatory cytokines IL-1β and IL-6. However, the increased proinflammatory status in denervated mice did not affect atherosclerotic lesion size or lesion composition. Conclusion: Predominantly selective Px of the spleen enhances the inflammatory status, which, however, does not aggravate diet-induced atherosclerotic lesion development.

Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells

“…At the heart of this debate is the apparent lack of vagal innervation to the spleen. While some studies have reported evidence of vagal innervation at the splenic poles in rodents(38), this remains controversial, and most current reports favor a mechanism in which efferent vagal signals are transmitted to the spleen via sympathetic nerves (this hypothesis however, has been also refuted(40)), which enter along the vessels of the splenic plexus, and/or via non neuronal acetylcholine signaling initiated by circulating T-cells which receive vagal input outside of the splenic parenchyma (41, 42). Both of these pathways are thought to result in activation of α-7-containing nicotinic receptors on splenic macrophages.…”

Ganoderic acid A against cyclophosphamide‐induced hepatic toxicity in mice

“…As far as we know, AST and ALT activities are widely used as key biochemical indicators to indicate the severity of liver injury . CP stimulation can significantly increase the serum transaminase level, and GAA intervention can improve the serum transaminase level.…”

Ameliorative Effect of Dangguibuxue Decoction against Cyclophosphamide-Induced Heart Injury in Mice

“…As a part of the mononuclear phagocyte system, the spleen can be regarded as a large lymph node, because its absence usually leads to a predisposition to infections [ 20 ]. Meanwhile, it has been reported in mice that half of the body's monocytes are reserved within the red pulp of spleen [ 21 ]. When tissue damage happened, these monocytes would move to injured tissue transforming into dendritic cells and macrophages to facilitate the treatment of tissue.…”