The Combined Therapy And Immunological Mechanism Of Low Dosage Thalidomide In The Treatment Of Crohn's Disease

Background and Purpose Crohn'S disease(CD)is a chronic nonspecific inflammation that affect the entire digestive tract and almost all organs such as skin,joints,eyes,etc.The incidence of CD has been increasing rapidly in China in recent two decades.The current medications(including hormones,immunosuppressants,and biological agents)were only able to control the condition and not able to cure CD.It is reported that thalidomide(THD)could inhibit TNF-a activities and had promising clinical response among part of CD patients,offering another treatment option.But its mechanisms were not completely revealed and there are also high incidence of side effects,which increase over dosage accumulation and often used as combited therapy,which might affect its efficacy and safety effect.Usage of low dosage of thalidomide is thought to have relatively low incidence of side effects.In this paper we address the efficacy and safety of low dosage THD combited with other medications in treating patients with CD.Besides,we used DSS to induce IBD mice model to further analyse the immunological mechanism of THD in the treatment of CD.Method:Clinical data of CD patients,hospitalized in Nanfang hospital,the first affiliacted hospital of Southern Medical University from January,2012 to December,2016 were retrospectively analized.We set THD along as control group and THD+azathioprine(AZA),THD+hormone,THD+IFX as study group and evaluated them with clinical respon rate,clinical remission rate,incidence and severity of adverse effect.We used DSS to induce IBD mice model,with the control group given water that contain 2.5%DSS and DMSO through intraperitoneal injection,while the treatment group received THD through intraperitoneal injection instead of DMSO.HE staining was used to analyse mucosal changes and flow cytometry was used to analyse the effects of THD on different cell lines.Spss21.0 statistical software was used to analyze the data of t test,univariate and multivariate analysis of variance,P<0.05 was statistically significant.Result:A total of 62 cases of CD patients were included in this study,there were 36 males and 26 females.The clinical remission rate of group THD,THD+AZA,THD+hormone,THD+IFX were 40.0%,53.8%,66.7%,71.4%,while their incidence of adverse effect were 60.0%,92.3%,83.3%,71.4%.75%of CD patients that had fistula complication achieved complete healing after treating with THD+IFX.Thalidomide had therapeutical effect on DSS induced mouse model of IBD and promotes the healing of mucosa by promoting the polarization of macrophages.THD inhibits the polarization of CD4+T cell,but not did proliferation.Conclusion:In group control study low dosage THD,IFX group had the best therapeutical effect without increasing the severity of adverse effect.Hormone and AZA could increase the clinical remission rate of low dosage THD but increased its side effect at the same time,especially AZA.Low dosage THD+IFX had promising healing rate for patients with fistula complication.THD has therapeutical effect on DSS induced mouse model of IBD and promotes the healing of mucosa by promoting the polarization of macrophages and inhibits the polarization of CD4+T cell.