Changes Of Serum Cytokine Profile In Active Systemic Lupus Erythematosus And Its Relationship With Organ Damage

Objective: Systemic lupus erythematosus(SLE)is a highly heterogeneous autoimmune disease,and its pathological mechanism involves autoantibodies,immune complex deposition and cytokine imbalance.It often has multiple organ or system damage,and the prognosis varies greatly.In this study,we analyzed the relationship between cytokine profile and disease activity or organ damage by observing the change of serum cytokines in patients with SLE in different stage,in order to screen the serum markers of SLE and disease activity in early stage,then to provide more basic data for accurate prevention and treatment of organ injury.Methods: Patients with active SLE hospitalized in the Department of Rheumatology and Immunology,the second Hospital of Hebei Medical University from October 2019 to January 2021 were collected.All patients met the diagnostic criteria of the American Society of Rheumatology in 2009 or the criteria of the International Cooperative Clinic of systemic Lupus Erythematosus in 2012,and the Systemic lupus erythematosus disease activity(SLEDAI)-2000 score was more than 4.The patients were divided into different subgroups according to the history of treatment,the degree of disease activity,the course of disease,Systemic Lupus International Collaborating Clinics,SLICC/American College of Rheumatology Damage Index(SDI)and systemic involvement.The changes of cytokine expression and the relationship between cytokine expression and disease activity severity and organ involvement were statistically analyzed.Results:1.The levels of TNF-α、IFN-α、IL-1β、IL-8、IL-12p70、IL-2、IFN-γ、IL-4、IL-5、IL-6、IL-17、IL-10 and the ratio of Th1 and Th2 related cytokines expression were higher than those in the control group(P<0.05 or P<0.01);compared with the initial treatment group,the levels of IL-5 and IL-17 in the recurrence group increased,and the levels of IFN-α,IL-10,and IL-8 decreased(P<0.05 or P<0.01).2.Compared with the recurrence group,the levels of IgG,IgA,IgM,and anti-ds DNA antibody(ELISA method)in the initial treatment group increased,and the level of complement C4 decreased(P<0.05 or P<0.01).3.Compared with the mildly active group,the levels of IL-4 and IL-8 in the moderately active group were significantly increased,and the levels of TNF-α,IFN-α,IL-8,IL-4,IL-6,IL-10 and IL-17 in the severely active group were significantly increased(P<0.01),and the levels of IFN-α and IL-6 in the severely active group were significantly higher than those in the moderately active group(P<0.01).There is a positive correlation between the levels of IFN-α,IL-8,IL-6,IL-10 and SLEDAI score.4.Divided into two groups according to SDI,the average age of> 1 group was significantly higher than that of ≤ 1 group(P<0.01),and the levels of IL-8,IL-6,IL-17 and IL-10 in > 1 group were significantly higher than those in ≤ 1 group(P<0.01).5.Recurrent patients were divided into two groups according to the course of disease.The average age of > 60 months group was significantly higher than that of ≤ 60 months group(P<0.01);compared with ≤ 60 months group,the level of IFN-α、IL-8、IL-2、IFN-γ、IL-5 in> 60 months group decreased(P<0.05 or P<0.01).6.Compared with the group without renal involvement,the IFN-α,IL-8,IL-10 levels in the renal involvement group increased,and the levels of IL-17/IL-10 were lower(P<0.05 or P<0.01);compared with the group without hematological involvement,the levels of IL-8and IL-10 in the hematological involvement group were significantly higher(P<0.01),and the levels of IL-17 and IL-17/IL-10 were significantly lower(P<0.05);compared with the non-nervous system involvement group,the nervous system involvement group IL-10 levels were significantly increased(P<0.01),and IL-4 levels were significantly reduced(P<0.05);compared with the non-pulmonary interstitial disease group,the levels of IL-12p70 and IL-6 in the pulmonary interstitial disease group increased(P<0.01、P<0.05),and the level of IL-10 decreased(P<0.05).Conclusions:1.Various cytokines secreting by multiple immune cells exist in the blood of patients with active SLE.Macrophage related cytokines including IFN-α and IL-8 maybe trigger the onset of SLE and they are closely related to the severity of disease activity in SLE.The activation of Th17 cells was more prominent when the disease recurred.2.The expression of cytokine’s superiority maybe decide are related to different involved organs.These implied that the immune mechanisms causing damage of target organs were different.The cytokines related to Macrophage,such as IFN-α,IL-8 and IL-12p70,should be paid more attention in active SLE.