Abstract
Background Rheumatoid arthritis (RA) is a chronic systemic chronic autoimmune disease characterized by the aggregation of immune cells and secretion of cytokines in the joint synovium, causing hyperblastosis and even bone destruction. Acupuncture has been proven effective in RA treatment. This study aimed to investigate the anti-inflammatory action of acupuncture, specifically, in relation to immune cell interactions and key mediators. Methods Rats with adjuvant-induced arthritics (AIA) were treated with manual acupuncture (MA) at Zusanli (ST36). Joint edema and paw withdrawal latency were monitored to observe the effects on inflammation. The levels of 24 cytokines, chemokines, and growth factors in ankle joints during the treatment (on days 1, 7, 15, and 21) were detected by multiplex immunoassay. A bioinformatics analysis based on a directed weighted mathematical model was used to construct cell communication network diagrams and identify the key cells through calculation. The monocyte/macrophage polarization in inflamed joints was investigated by detecting M1- and M2-phenotypic populations and their related cytokines. Results ST36 MA alleviated paw edema and upregulated the nociceptive threshold of AIA rats. Several innate and adaptive immune cytokines were dynamically regulated by MA, and MA-treated rats showed a significant improvement in symptoms compared with AIA rats by day 21. The immune cell-cell communication networks were intensified with the development of RA but were significantly reduced after treatment with MA. MA was found to specifically regulate monocytes/macrophages in inflamed ankle joints ST36 MA also inhibited M1-phenotype macrophages accompanied by decreased levels of IL-1β. Conclusions ST36 MA showed anti-inflammatory and analgesic effects as well as inhibition of immune cell communication networks in inflamed joints of AIA rats. Inhibiting the polarization of macrophages to the M1-phenotype in inflamed joints may be one of the key mechanisms of MA anti-inflammatory action. This research highlighted a systematic research paradigm for investigating mechanisms of acupuncture action.
Highlights
Rheumatoid arthritis (RA) is a chronic systemic chronic autoimmune disease characterized by the aggregation of immune cells and secretion of cytokines in the joint synovium, causing hyperblastosis and even bone destruction
Chemokines, and related growth factors are key modulators of both homeostasis and inflammatory processes [2, 3]. e binding of these mediators to their cognate receptors triggers a cascade of cellular signaling events to regulate various cellular functions, such as proliferation, cell adhesion, apoptosis, phagocytosis, cytokine secretion, and angiogenesis [4]. e robust functioning of the immune system depends on a complex multilevel interaction network, connecting intracellular biochemical pathways, intercellular communication networks, and organ-cellular trafficking through time and space. erefore, the investigation of the networks of inflammatory cells and secreted cytokines controlling inflammation and inflammatory disorders has attracted much attention [5, 6]
We found that manual acupuncture (MA) at ST36 could downregulate several innate and adaptive immune cytokines in serum of adjuvant-induced arthritic (AIA) rats, a commonly used RA model [13]
Summary
Rheumatoid arthritis (RA) is a chronic systemic chronic autoimmune disease characterized by the aggregation of immune cells and secretion of cytokines in the joint synovium, causing hyperblastosis and even bone destruction. Is study aimed to investigate the anti-inflammatory action of acupuncture, in relation to immune cell interactions and key mediators. E monocyte/ macrophage polarization in inflamed joints was investigated by detecting M1- and M2-phenotypic populations and their related cytokines. ST36 MA showed anti-inflammatory and analgesic effects as well as inhibition of immune cell communication networks in inflamed joints of AIA rats. Inhibiting the polarization of macrophages to the M1-phenotype in inflamed joints may be one of the key mechanisms of MA anti-inflammatory action. Studies of the anti-inflammatory effects of acupuncture have focused primarily on specific cells and their related cytokines, rather than analyzing its potential regulatory effects on the immune network and the key cells involved [8,9,10]
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