Effect Of IL-15 On Peripheral Blood Mononuclear Cells In Patients With Knee Osteoarthritis

Objective:Arthritis(OA)is a global chronic degenerative joint disease,especially in China,which is gradually entering the aging society.The pathophysiology of OA is complex and far from being understood.However,OA in the early stage,it has different degrees of inflammatory nature,the internal process of joint not only includes decomposition,but also anti-inflammatory and anabolic process.This phenomenon is driven by various mediators,and the key role is mediated by the interaction between immune cells and cytokine network.Some experiments also showed that a large number of NK cells infiltrated into the synovium of OA patients,and the proportion of NK cells increased with the increase of the severity of the disease.At the same time,the activation degree of NK cells also further increased,suggesting that NK cells are indeed involved in the occurrence and development of OA.However,we found that the level of IL-15 in patients with KOA was higher than that in healthy controls,objective to investigate the changes of serum interleukin-15(IL-15)in patients with knee osteoarthritis(KOA)and healthy controls.The effect of IL-15 on the expression of natural killer(NK)cell receptor in peripheral blood of patients with KOA and healthy controls,as well as the secretion of TNF-αand IFN-γby peripheral blood mononuclear cells(PBMCs).Methods:Peripheral blood samples were collected from 30 patients with KOA and 35 age-matched healthy adults as controls.PBMCs were cultured in the presence or absence of IL-15(10ng/ml)for 24 hours,CD3~-CD56~+ lymphocytes were detected by flow cytometry.In the presence or absence of IL-15,100μL PBMCs cell suspension(5000 cells/well)was inoculated into 96 well plate for 24 hours,and the absorbance at 450 nm was measured by enzyme reader.The levels of IL-15 in blood supernatant and TNF-αand IFN-γwere detected by enzyme-linked immunosorbent assay(ELISA).Results:1.We observed that the level of serum IL-15 in patients with KOA was significantly higher than that in healthy controls.2.IL-15 can enhance the expression of NK cell receptors CD69,CD94 and NKG2D in patients with KOA.3.The levels of TNF-αand IFN-γin the supernatant of KOA patients were significantly higher than those of healthy controls.Conclusion:The increase of IL-15 in peripheral blood of patients with KOA may be an important link in the occurrence and development of KOA,One is to increase the expression of receptors on the surface of NK cells,so as to improve the cytokine secretion and cytotoxicity of NK cells,The second is to participate in the occurrence and development of KOA disease by promoting the increase of TNF-αand IFN-γ levels.Therefore,IL-15 antagonist may have therapeutic effect on KOA patients.IL-15 antagonist may be a new therapeutic option to prevent or delay the progression of KOA.