The Effects of Moxibustion on PD-1/PD-L1-Related Molecular Expression and Inflammatory Cytokine Levels in RA Rats

Abstract

Objective. Rheumatoid arthritis (RA) is an autoimmune disease that starts with inflammation of the synovium. The pain and joint dysfunction caused by RA urgently need an effective treatment to alleviate the inflammatory reaction and delay the progression of the disease. The pathological damage of RA is proposed to associate with the dysfunction of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway. Moxibustion, as a main complementary therapy of traditional Chinese medicine (TCM), has been proved effective to reduce chronic inflammatory reaction on RA, but whether the anti-inflammatory effects are mediated by PD-1/PD-L1 pathway is still unclear. Therefore, moxibustion was conducted in the rats with RA to investigate its effect on PD-1/PD-L1. Methods. The rats' right hind paws were injected with Freundʼs complete adjuvant (FCA) to establish the model of RA. Seven days after the injection of FCA, moxibustion therapy was performed on the acupoints of Shenshu (BL23) and Zusanli (ST36) once a day for three weeks. Then, ELISA and immunohistochemical methods were used to analyze the influence of moxibustion on the expression of PD-1/PD-L1. If the moxibustion had an effect on the expression of PD-1/PD-L1-related molecules, we would knock down PD-1 with adenovirus vector. After moxibustion therapy, ELISA and histological analysis were performed to observe the anti-inflammatory effect of moxibustion. Results. The results demonstrated that moxibustion had an effect on the expression of PD-1-related molecules. The results of ELISA manifested that moxibustion decreased the level of IFN-γ and increased the level of IL-4 and IL-10. HE staining revealed that moxibustion alleviated the proliferation of synovial tissue. However, the anti-inflammatory effect and pathological improvement were weakened when PD-1 was blocked. Conclusions. The results indicate that moxibustion affected the expression of PD-1/PD-L1-related molecules and can effectively treat RA damage. The anti-inflammatory effect of moxibustion was weakened when PD-1 was knocked down.

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“…Although non-steroidal anti-inflammatory drugs, glucocorticosteroids and biological agents (such as etanercept, infliximab and adalimumab.) have their own advantages in the treatment of RA, they also have a slow onset of action, are prone to relapse when stopped, are expensive, can induce gastrointestinal reactions and increase the risk of cardiovascular disease ( 49 ). It is therefore important to actively investigate alternative therapeutic approaches, such as complementary and alternative medicines, in addition to conventional medication.…”