The Role Of Interleukin-6 In The Pathogenesis Of Ankylosing Spondylitis Disease Activity And Efficacy Assessment

PartⅠ:Clinical Study of methylprednisolone in Active Ankylosing SpondylitisObjective:1.To evaluate the efficacy and safety of methylprednisolone(MP) in ankylosing spondylitis(AS).2.To understand the change of AS disease activity after MP therapy.Methods:This was an open-labeled,two-center trial.Subjects eligible for this study were adults with a diagnosis of definite AS.After using stable NSAIDs and DMARDs for three months,the disease still was active.Active disease was a Bath AS Disease Activity Index(BASDAI)≥4, spinal pain VAS≥4,ESR≥30mm/h and CRP≥1.5 normal.Concurrent stable treatment with nonsteroidal anti-inflammatory drugs(NSAIDs) cytotoxic drugs,or disease -modifying anti-rheumatic drugs was permitted during the study.Subjects were not permitted to be on systemic corticosteroids for 1 month before screening.MP were given as 3 intravenous infusions, in single doses equivalent to 250-500 mg of MP.All patients were followed up to 3 weeks.The primary endpoint was proportion of ASAS20 responders at week 3.The secondary endpoints were the proportion of subjects achieving an ASAS partial remission,the change from baseline in Bath AS Functional Index(BASFI) and in the physical component summary score of the short form-36 in health survey questionnaire(SF-36) at week 4.Other secondary endpoints,related to reducing signs and symptoms of AS and improving range of motion and physical function,were evaluated.Rusults:1.Efficacy Results:After MP treatment of once,90.24%of patients reached the primary end point of ASAS20.The percent of patients reaching the secondary BASDAI50 were 51.21%.The improvements at week 4 of BASDAI,BASFI,BASMI,ESR/CRP were statistically significant.2.Safety Results:11(26.82%) patients reported 41 treatment related adverse events.The most frequently occurring were of the raise of serum glucose.It rose up from 5.3mmol/L to 5.9 mmol/L.The occuring of acne were in 4 patients and three patients had hydrosarca.A patient appeared stomach discomfort and the test of gastroscopy showed normal.A patient appeared vague of eyes.They were all better after drug withdrawal.3.Follow Up Study Results:39 patients who attained an improvement of＞ASAS20 at the end of the MP treatment were followed up.51.28%patients felt that symptom aggravated then before at the first consultation.Two patients of the total relapsed.The percent of patients who relapsed within 2,3and 6 months were 5.13%,12.8%and 7.69%respectively.Conclusions: 1.MP treatment could improve the clinical symptoms and sighs of patients quickly and markedly. Moreover,it could increase home range and improve quality of life of AS patients.The improving of clinical symptoms were most obvious after MP treatment once.2.The adverse effects of MP was minor and they occurred frequently in the second or the third week PartⅡ:The role of Interleukin-6 in ankylosing spondylitisObjective:1.To investigate if the level of Interleukin-6(IL-6) can be detected to judge the activity of ankylosing spondylitis(AS) and if it can be acted as the therapeutic effect index of AS.2.To investigate the relationship between the-174G/C polymorphism of gene and AS and the activity of AS.Method1.First of all,we evaluate the clinical parameters of 80 patients of AS,including the Bath AS disease activity index(BASDAI),Bath AS functional index(BASH),Bath AS metrology index(BASMI),night pain and quality of life,ESR,CRP were determined.2.The level of IL-6 was measured with ELISA.Then analyze if the level of IL-6 has correlation with some disease activity index.3.After treatment with medicine,the level of IL-6 was measured with ELISA.Then compare the level of IL-6 before and after treatment.Then analyze the level of IL-6 with some disease activity index.4.The-174G/Cpolymorphism of IL-6 gene was analyzed by polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP).Then investigate the relationship between the - 174G/C polymorphism of Interleukin-6(IL-6) gene and AS.ResultThe average age of AS group and control group were29±10.4 and 28.1±8.7.The male of AS group were 69,and the control group were 45.There were no significant difference(P＞0.05). The number of AS group which HLA-B27 were positive were 58,the number of the control group which HLA-B27 were positive were 1.There were significant difference(P＜0.05).Serum level of IL-6 was detected by ELISA.Compared with healthy group,IL-6 level was increasly obviously in AS(P＜0.05).After treatment,IL-6 level decreased.Baseline serum IL-6 level had positive correction with AS activity index.The GG genotype frequencies in the AS group and control group were 96.25%and 96.15%,The GC genotype frequencies in the AS group and control group were 3.75%and 3.85%,G alleles were not significantly higher in the AS group.ConclusionSerum level of IL-6 was increasly obviously in AS.IL-6 level was high correlated with BASFI, ESR and CRP,but was no correlation with -174G/C polymorphism of IL-6 gene.