2022, Vol. 26 ›› Issue (9): 1459-1466

Mechanism and prospects of regulating lymphatic reflux function in the treatment of rheumatoid arthritis

Zhang Lichuang1, 2, 3, 4, Xu Hao2, 3, 4, Ma Yinghui1, Xiong Mengting2, 3, 4, Han Haihui1, Bao Jiamin2, 3, 4, Zhai Weitao1, Liang Qianqian1, 2, 3, 4   

Abstract: BACKGROUND: In recent years, studies have found that pathological process of rheumatoid arthritis is closely related to the immune response in the articular cavity, but it is not clear how immune cells participate in and regulate the pathological changes of rheumatoid arthritis. In addition, the lymphatic vessels around the joint have the function of reflux inflammatory factors and immune cells, which are also closely related to the changes of intra-articular microenvironment. Therefore, the study on the relationship between lymphatic reflux function and intra-articular immune response has gradually become a hot topic in this field.
OBJECTIVE: To review the research on the regulation of lymphatic reflux function in the treatment of rheumatoid arthritis.
METHODS: Chinese and English search terms “Rheumatoid arthritis, lymphedema, lymphatic drainage, lymphatic system” were used to search the relevant articles on China National Knowledge Infrastructure, PubMed, and Web of Science from January 2000 to April 2021. Finally, 67 related articles were included for review.
RESULTS AND CONCLUSION: (1) The process of lymphatic reflow disorders exists in the process of rheumatoid arthritis. Severe people even experienced the lymphatic edema of the limbs. Targeted lymphatic reflux function can be used as a new intervention measures for treating rheumatoid arthritis. (2) Many studies have found that inflammatory responses in microenvironments can promote local lymphatic production. Tumor necrosis factor α secreted by macrophages causes lymphatic endothelial cells to produce endothelial growth factor C. Endothelial growth factor C acts on lymphatic endothelial cell proliferation, lymphatic tube increase, and lymphatic reflux compensatory reinforcement. (3) Long-term inflammatory response will inhibit lymphatic smooth muscle contraction. The mechanism may be that lymphatic endothelial cells highly express nitric oxide synthase, promote lymphatic endothelial cells to increase nitric oxide, which affects the contraction of lymphatic hemmus cells. (4) Immunization of lymphatic reflow mainly reflected in the formation of lymphatic tubes. The formation of lymphatic vessels is commonly regulated by macrophages and T cells. The known mechanism is that macrophages can secrete endothelial growth factor C to stimulate lymphatic production, and T cells secrete gamma-interferon to inhibit excessive proliferation of lymphatic tubes, but precise mechanisms still need further study. (5) In addition to basic research, many clinical reports have also pointed out that there is a phenomenon of lymphatic reflow disorders in rheumatoid arthritis. Even after joint replacement, this chronic lymphatic return barrier cannot be resolved. (6) Many basic studies have found that regulating lymphatic reflux will delay the process of rheumatoid arthritis, so the lymphatic tube is expected to be a new target for the treatment of inflammatory diseases. At present, the drugs that target lymphatic reflow disorders are still less. Only individual research finds that Etanercept Solutionfor, B cell depletion or local injection endothelial growth factor C can improve lymphatic return. Moreover, drugs with anti-phrochlorism have better efficacy to promote lymphatic return. The effective monomer composition in the future Chinese medicine may become targeted new drugs that promote lymphatic return.

Key words:rheumatoid arthritis, lymphoedema, lymphatic return, lymphatic system, arthroplasty, lymphatic endothelial cells, lymphatic muscle cells, review