The Function Of Interleukin-7 In Peripheral Blood Monocytes Of Healthy People And Rheumatoid Arthritis Patients

Background:Rheumatoid arthritis(RA)is a common autoimmune disease which will causes disability by damaging cartilage and bone,complicated with severe extra-articular manifestations.Patients could get a favorable prognosis by treated in the early stage.So it is important to diagnose RA and give therapeutics as early as possible.Interleukin-7(IL-7)is an important cytokine for the proliferation and differentiation of lymphocytes.Only small numbers of study showed that IL-7 and interleukin-7 receptor(IL-7R)may participate the inflammation process in human peripheral blood monocytes.Some study showed that IL-7/IL-7R may induced the secretion of tumor necrosis factor α(TNFa)by monocytes in the etiology of RA.So far,the function and mechanism of interleukin-7 in peripheral blood monocytes has not been defined.Objective:The study aimed to investigate the expression of IL-7/IL-7R and other inflammation-related cytokines in peripheral blood monocytes of healthy people and RA patients,and to definite the function of IL-7/IL-7R in monocytes.The study also explored the correlation of IL-7/IL-7R with the course of RA.Method:We collected the blood sample from healthy people,untreated RA patients and refractory RA patients.Compared the expression of CD 127 and other cytokines before and after the stimulate of lipopolysaccharide(LPS).The expression of IL-7Rα(CD127)and TNFa,IL-6,IL-10,interferon regulatory factor-4(IRF-4)were measured by flow cytometry and qRT-PCR.We used small interfering RNA(siRNA)to found the regulation function of CD 127 for other cytokines.Linear-regression analysis was used to find the correlation of CD 127 and TNFa.Result:In healthy people:The expression of CD 127 was low in human monocytes.After the stimulation of lipopolysaccharide(LPS).some monocytes showed significantly increased expression of CD127.These monocytes also showed high expression of TNFa,IL-6,IL-10,IRF-4.The expression of these cytokines kept increasing during six hours after the stimulation of LPS,then decreased to the normal range after 18 hours.After the stimulation of LPS.the expression of CD 127 in monocytes originate from all three human monocyte subsets showed non-significant differences.After inhibiting the expression of CD127.the expression of TNFa and IL-6 was lower than the negative control,whereas the expression of IL-10 and IRF-4 was higher.In RA patients:The expression of cytokines in monocytes from untreated RA patients was similar to healthy people.The expression of CD127 as well as TNFa,IL-6,IL-10 were higher in refractory RA patients than in healthy people.CD 127 in monocytes of refractory RA patients also showed a cross tolerance of LPS.The correlation analysis between CD 127 expression and IL-6 or TNFa expression showed that the expression of CD 127 positively correlated with both TNFa and IL-6 expression.After anti-TNFa treatment,the expression of CD127 as well as TNFa decreased significantly.Conclusion:In healthy people:1.LPS can induce the expression of IL-7/IL-7R on human monocytes and in a time-dependent manner.2.The expression of IL-7/IL-7R in monocytes originate from all three human monocyte subsets showed non-significant differences.3.IL-7/IL-7R can induce the expression of IL-10 and IRF-4,whereas reduce the expression of TNFa and IL-6 in monocyte.In RA patients:1.The expression of IL-7/IL-7R in monocytes of untreated RA patients was similar to healthy people.2.The expression of IL-7/IL-7R showed correlation with TNFa.IL-7/IL-7R expression on blood monocytes may be used as a severe marker for RA patients.3.TNFa showed a feedback for the regulation of IL-7/IL-7R in monocytes of RA patients.