The Impacts Of Qing-Xin-Pei-Tu Therapy For Atopic Dermatitis On IL-2/TNF-α And Their Receptors And Evaluation Of Its Therapeutic Efficiency

Since 1992,Sheehan etc.published a series of clinical randomized controlled trials in "Lancet" and "British Journal of Dermatology"about TCM (Traditional Chinese Medicine) treatments of atopic dermatitis which sugested TCM treatments may be effective on atopic dermatitis.From then on TCM treatments as a potential effective method of treatment was used for the clinical and experimental researchs of atopie dermatitis more and more.The effects and mechanisms of Qing-Xin-Pei-Tu therapy were researched from the points of view including literature studies of TCM treatments of atopic dermatitis,sequential trials and longer-term follow-up observations, as well as the immunological mechanisms in this paper.PartⅠLiterature studiesObjectiveTo explore the basic etiology and pathogenesis of atopic dermatitis. Analysis of the laws of TCM syndrome differentiation of atopic dermatitis. Explanation of Qing-Xin-Pei-Tu therapy which was a TCM treatment strategy of check and balance between Heart and spleen on atopic dermatitis.MethodsAccording to historical literature analysis of the understanding of TCM on atopic dermatitis.According to history of medicine,combined with the characteristics and clinical features of atopic dermatitis,analysis of the leading pathogenesis and therapeutic methods.To collect published treatment literature of atopic dermatitis about Chinese herbal formula.Analysis of the laws on syndrome differentiation of atopic dermatitis by the methods combined with differentiation of Zang and Fu and the predictive diagnosis of syndromes by the effects of herbal prescription treatment.ResultsEtiology of atopic dermatitis was largely attributable to intolerance, ]eft heat and toxins during gestationa]period from Chinese medical viewpoint.The leading pathogenesis was cross-cutting between heart-fire and insufficiency of the spleen.Heart-fire could result in insufficiency of the spleen.Insufficiency of the spleen could result in heart-fire.A mixed situation was made by the cross-cutting between heart-fire and insufficiency of the spleen.Formulas of differentiation of symptoms and signs of atopic dermatitis were focused on the use of drugs for heart channel.Formulas of differentiation of disease were focused on the use of drugs for the liver channel.Formulas of Japanese Kampo treatment were focused on the use of drugs for pulmonary channel.The spleen channel was the most important target for therapy in all Formulas.There were significant negative correlations between heart and spleen,liver and spleen,liver and kidney,spleen and pulmonary separately (P＜0.05,P＜0.01,P＜0.01,P＜0.01).Qing-Xin-Pei-Tu therapy was focused on the relationship of check and balance between heart and spleen and emphasised on co-existence of Qing-Xin therapy and Pei-Tu therapy.At the same time,it also stressed that Jianpi drug and Xiexin drug were complimentary each other.ConclusionsEtiology of atopic dermatitis was largely attributable to intolerance, left heat and toxins during gestational period.The leading pathogenesis was cross-cutting between heart-fire and insufficiency of the spleen.The spleen channel was the most important target for treatment of TCM on atopic dermatitis.Qing-Xin-Pei-Tu therapy was basic Chinese traditional treatment on atopic dermatitis with its own distinct characteristics..It is particularly suited to treat the complex cases accompanied with cross-cutting between heart-fire and insufficiency of the spleen. PaTtⅡClinical studiesObjectiveTo evaluate the reliability of SCORing Atopic Dermatitis index(SCORAD) for atopic dermatitis.To evaluate the short-term and long-term effect of combined therapies of traditional Chinese medicine and Western medicine on patients with atopic dermatitis.MethodsThe internal correlation analysis of SCORAD index:Evaluation of severity of the disease in patients with atopic dermatitis using SCORAD index and the internal correlation analysis of the three individual parts in SCORAD index as well as the correlation between the three individual parts and the total score.Sequential analysis test:The primary efficacy parameter was the SCORAD index.The effect was evaluated by Sequentialanalysis test after the patients had treated by combined therapies of traditional Chinese and Western medicine for one month.Follow-up analysis:Out-patients with atopic dermatitis were followed up by telephone who had visited dermatology department in our hospital during February 2005 to October 2007 period.Patients or patients' family members were asked about patients' condition in detail around three topic including basic recovery,improvement and invalid.The long-term effect of Qing-Xin-Pei-Tu therapy used for treatment on atopic dermatitis were evaluated on the whole.ResultsThe internal correlation analysis of SCORAD index:The internal correlations between spread of lesions and intensity of lesions or SCORAD index were significantly(r=0.541,0.743 separately:P＜0.002,0.000 separately). The internal correlations between spread of lesions and sujective symptom was not significantly(r=0.296,P＞0.05).The internal correlations between sujective symptom and SCORAD index was significantly(r=0.704;P＜0.000).Sequential analysis test:After the seventh petient had been treated,the effect of combined therapies of traditional Chinese and Western medicine was affirmed for patients with atopic dermatitis.Follow-up analysis:A total of 18 cases of patients with atopic dermatitis who had stopped treatment from 3 months to 22 months were followed up.As a result,5 cases cured,8 cases improved and 5 cases were invalid.Recovery rate was 27.78%.Effective rate was 72.22%.ConclusionsSCORAD index was used for assessing the condition of atopic dermatitis with good internal consistency and reliability.SCORAD index was used for assessing the condition of atopic dermatitis in this study achieved good results.The short-term effect of combined therapies of traditional Chinese and Western medicine based on Qing-Xin-Pei-Tu therapy were affirmed for patients with atopic dermatitis.The therapeutic schedule had a good long-term effect and could help atopic dermatitis sufferers control their condition,reduce relapse,reduce the usage quantity of topical steroid and antihistamines.PartⅢExperimental study and analysis of clinical significanceObjectiveResearches sugested that natural immune system and regulatory T cells might play an important role in atopic dermatitis pathogenesis in recent years.There were close relationship between Th1/Th2 polarization and natural immune system or regulatory T cells.In this study,serum interleukin-2(IL-2) and soluble interleukin-2 receptors(sIL-2R),tumor necrosis factor(TNF)-αand soluble tumor necrosis factor receptors(sTNFR) were detected as a entry point to study the immune status of CD4+CD25+ regulatory T cells and the natural immune system in patients with atopic dermatitis.The patient's immune disorders and their correlations with the patient's condition were discussed.To investigate the effective mechanisms of combined therapies of traditional Chinese and Western medicine on atopic dermatitis,the patients' conditions and the immune status changes were also discussed after the patients treated by combined therapies of traditional Chinese and Western medicine based on Qing-Xin-Pei-Tu therapy.MethodsSerum IL-2 and slL-2R levels were detected by enzyme-linked immunosorbent assay(ELISA).The disease severity was assessed by SCORAD index.The relationships of IL-2 and slL-2R to SCORAD and course of disease were evaluated.SerumTNFαand sTNFR levels were detected by ELISA.The disease severity was assessed by SCORAD index.The relaLionships of TNF-αand sTNFR to SCORAD and course of disease were evaluated.Patients with atopic dermatitis were enrolled into this study before and after treated by combined therapies of traditional Chinese and Western medicine for one month.Serum IL-2,slL-2R,TNF-α,sTNFR levels were detected by ELISA.The disease severity was assessed by SCORAD index.Results30 patients with atopic dermatitis and 20 normal human controls were enrolled into this study.Before treatment,Serum IL-2 levels were decreased compared with the controls(P＞0.05),while Serum sIL-2R levels were significantly increased in patients with atopic dermatitis(P＜0.05).Serum sIL-2R levels showed a significant positive correlation with the spread of lesions and inverse correlation with course of disease(r=0.37 and -0.398 respectively;all P＜0.05).30 patients with atopic dermatitis and 20 normal human controls were enrolled into this study.Before treatment,serum TNF-αlevels were mildly decreased compared with the controls(P＞0.05),while Serum sTNFR levels were significantly increased in patients with atopic dermatitis(P＜0.001).Serum sTNFR levels did not showed a correlation with the SCORAD and course of disease (all P＞0.05).The state of illness were compared before and after treatment in 9 patients with atopic dermatitis.After treatment for one month,serum IL-2,slL-2R and SCORAD in patients in this study were significantly increased(P＜0.05)and sTNFR levels significantly decreased compared with before treatment.The variable of TNF-αlevels no significantly difference(P＞0.05).Serum sTNFR levels did not showed a correlation with the SCORAD and course of disease(all P＞0.05).ConclusionsThe increased serum levels of sIL-2R in patients with atopic dermatitis had a positive correlation with the spread of lesions and negative correlation with course of disease.Elevated serum sIL-2R in patients with atopic dermatitis might increase the ability of binding IL-2 and lead to immune disorders.This mechanism might play a role in disorder of immune mechanism of atopic dermatitis or persistent activity of patient's condition.The increased serum levels of sTNFR in patients with atopic dermatitis might enhance the ability of binding TNF-αand reduce anti-infective and anti-inflammatory ability mediated by TNF-α.This mechanism might play a role in the pathogenesis of atopic dermatitis.The levels of Th1 type cytokines and the activity of TNF-αcould be promoted but the levels of sTNFR could be decreased by combined therapies of traditional Chinese and Western medicine based on Qing-Xin-Pei-Tu therapy.The therapeutic schedule was effective for patients with atopic dermatitis.