Regulation Of Immune Medicine And SLE Infection

BackgroundSystemic lupus erythematosus(SLE) is an autoimmune disease. It is a kind of diffuse connective tissue disease characterized by producing a variety of antibodies and immune response mediated inflammation. It related to involvement of several visceral organs. The condition ranges from mild to severe. In recent20years, the cyclophosphamide (CTX) and corticosteroid therapy were used as a classic method for the induction therapy of heavy SLE internationally. Lupus crisis often need combined with CTX, the impact of large dose methylprednisolone and immune globulin or three treatment. At present, there are many new advances in the treatment of SLE. However, the treatment is still dominated by hormone and immunosuppressant at home and abroad. They can effectively control the disease activity, improve the condition and the survival rate of patients with SLE. But the side effects of high dose immunosuppression and hormone can not be ignored. Many clinical studies showed that more than20%of the patients with high dose CTX, methylprednisolone treatment can occur the symptoms of infection, such as herpes zoster, pneumonia, urinary system infection and meningitis. Especially, the probability of complications in the immunocompromised patients after treating with pulse therapy increased greatly.The infection has become one of the main causes of death in patients with SLE.In recent years, the role of Chinese medicine in the treatment of SLE has caused some medical attention, In the ancient literature of traditional Chinese medicine, although there is not the same discussion named systemic lupus erythematosus disease, the similar or related is discussed extensively. After thousands of years of accumulation, the paper discusses involved the different aspects about SLE. According to its clinical symptoms, many Chinese scholars will it belongs to "HuDieBan","Yin and Yang poison","Sun boils" category. In the current domestic physician of TCM have knowledge about SLE, most believe that the foundation of this disease is inadequate natural endowment. So filling its deficiency account for important position in the study of SLE. Representative drugs such as Liuwei dihuangwan, Bailing capsule and so on.Liuwei dihuangwan is Yin and Yang on behalf of the party with Ziyin kidney function. The prescription Composed of Radix rehmanniae, Cortex Moutan, Oriental waterplantain rhizome, dogwood, yam, Poria six taste medicine.In the prescription Radix rehmanniae is on nourishing kidney essence role mainly, with dogwood nourishing liver and kidney and astringing essence, with Yam tonifying spleen and kidney and solid essence. Poria cocos light infiltration spleen wet to help Yam tonifying spleen. Poria cocos ooze water wet, making water the downward and out of body. Alisma discharge kidney fire and prevent the Rehmannia greasy. Cortex Moutan cleare liver fire, cool blood stasis, in addition to the bone steaming hot and wet of dogwo. The curative Effect of this prescription is exact after hundreds of years for medical use. This prescription is aigorous and become the representative prescription of nourishing kidney yin. Modern pharmacological studies confirmed: Rehmannia glutinosa have excited or adjusted adrenocortical axis function.lt can antagonize the inhibition of exogenous hormone on pituitary adrenal, delay liver decomposition of cortical hormone, and prompte the cortical hormone of the blood elevated. It can keep the physiological effects of glucocorticoid and reduce the side effects of glucocorticoid induced also.Bailing capsule consists of Artificial Cordyceps mycelium.It is consistent with natural Cordyceps sinensis, and has nourishing the lung and kidney, Yijing gas effect. Recent studies suggest that caterpillar fungus has antioxidant effect, improve organism cellular immunity, and reduce the side effects caused by glucocorticoid in protein decomposition and infections. It has the function of bidirectional regulation of human immune cells, can reduce the immunosuppressive drug side effects,but also have synergistic effect with immunosuppressive drugs. Cordyceps has good anti-inflammatory and immunomodulating effects, no hormone kind of side effects. The research reports about the Bailing Capsule Combined with Liuwei dihuangwan reducing the side effects caused by glucocorticoid and immune agents in SLE patients are few, especially on the intervention study of SLE complicated with infection. In the clinical practice of the past few years, we have been trying to give Liuwei dihuangwan combined with Bailing Capsule in treating SLE patients. Results showed that, increasing the above treatment can effectively reduce the risk of infection and can reduce the degree of infection in SLE patients; but also improve the clinical efficacy, reduce the mortality rate. Therefore, we did this research.Objective1. to learn about the risk factors of systemic lupus erythematosus (SLE) patients complicated with infection and the infections in two groups after the treatment, observating the intervention effect about regulation of immune medicine (bailing capsule and Liuwei Dihuangwan) on the SLE patients with immunosuppression and hormone therapy. So as to explore the therapeutic regimen of reducing SLE infection, looking for the effective and relatively safe ways for the treatment of SLE.2. to observate the expression levels of IL-2in two groups before and after treatment, concluding the possible mechanism of immune medicine reducing SLE infection in cellular immune.Methods1. Analysis of SLE patients with risk factors for infectionRetrospective study of82cases of patients with SLE on our hospital from January1,2010to December31,2012. The variables include gender, age, body mass, disease course, white blood cell, HGB, plasma albumin level, value IL2, C3, CRP, immune inhibitors and hormone application. To observe the incidence of infection and the correlation between the incidence of infection with these variables. In this study, the infection include bacterial infection, viral infections, fungal infection, involving the respiratory system, urinary system, skin and soft tissue, the central nervous system and blood system,etc.2. To observe the clinical curative effect and infection of two groups.2.1Retrospective study from the January1,2010to December31st,2012was associated with61cases of SLE patients with renal involvement and or interstitial lung disease (from the standard hospital treatment and regular follow-up of patients, selected cases that do not merge infection at first diagnosed). According to the severity of the disease were randomly divided into two groups. There were31cases in the Chinese and Western medicine treatment group, including4males,27females, age13to65years old, and average duration is36.2months. The western medicine control group contain30patients, including2males,28females, age14to63year old, and average duration is35.8months.2.2Method of administrationThe western medicine control group:The western medicine control group are given with glucocorticoid and cyclophosphamide therapy. A、glucocorticoid: prednisone(lmg/kg/d) is usually one-time taking in the morning, after two weeks in stable disease or eight weeks, then began to slow reduction at the rate of10%every two weeks until the prednisone0.5mg/kg/d, and treatment of hormone doses as far as possible little to10mg/d. In the reduction of drug in the process, if the condition is not stable, can temporarily maintain the original dose. B、 cyclophosphamide:once a month in the first half of the year after stability to every march(the dosage of16-20mg/kg added into250ml physiological saline for intravenous drip, generalty erery day0.4-0.6g, stay for two days). To the serious cases,we can use large dose (prednisone≥2mg/kg/d) and methylprednisolone pulse therapy. MP available to500-1000mg, one times a day, adding5%glucose slow intravenous drip for one to two hours, for three consecutive days to one course of treatment, treatment interval between five to thirty days. Oral prednisone (lmg/kg/d-2mg/kg/d) are used during interval or after pulse therapy. The course of treatment and interval length depend on the specific disease.The Chinese and Western medicine treatment group:on the basis of the western medicine plus Liuwei Dihuagnwan(8pills, three times a day) and Bailing Capsule(1.0g, three times a day).2.3Observation index:Through the observation of ESR, CRP, C3, C4, IG, ANA, ds-DNA, SLEDAI score, blood routine test, liver and kidney function, to compare curative effect of two kinds of therapy and the infection (pulmonary infection, urinary tract infection, infection of the central nervous system,etc.). Two groups both were treated for18months, and assessed at6,12,18months after the treatment.3. Effect of Bailing Capsule Combined with Liuwei Dihuagnwan on serum IL-2level in patients with SLE.Respectively in the two groups of patients at the first diagnosis and treatment of6,12,18months later, the conventional separation of peripheral serum3ml, then save it in the spare-80°C. According to the test operation provided by IL-2kit instructions, testing the patients’ serum level of IL-2.Results1. The study found that the risk factors of SLE patients with infections include defect of complement (Complement C3), immune abnormalities (Blood leukocyte count、Plasma albumin levels),disease activity, hormone impact, long-term immunosuppressive therapy, number of the affected organs, duration of hospitalization. They have significant difference by statistics analysis(P<0.05). Infection had no correlation with sex, age, body mass, and disease duration (P>0.05). The active parts of SLE with infection mainly concentrated in the respiratory tract and urinary tract. The pathogenic bacteria were mainly gram-negative bacteria. Conditional pathogenic bacteria is relatively more. 2. The total effective rate of treatment group (83.8%) was higher than that of the control group (73.3%), the difference was statistically significant. After6treatment months in treatment group the infection rate was9.67%, control group16.67%.After12treatment months, the infection rate was12.9%, control group20.8%;18months later, the infection rate was16.67%in treatment group, control group25.00%. The infection rate of treatment group was significantly lower than the control group(P<0.05).3. The level of IL-2of the treatment group was significantly higher than the control group.6months,12months,18months later, interleukin2levels of treatment group respectively were6.97±1.32pg/ml,7.26±1.25pg/ml,7.54±1.24pg/ml. Interleukin2levels of control group respectively was5.29±1.26, pg/ml,5.42±0.99pg/ml,5.63±1.15pg/ml. There was statistical significance between the two groups (P<0.05). The levels of IL-2before treatment was5.39±1.06pg/ml in the control group, the treatment group5.41±1.03pg/ml.Conclusion1.The immunosuppressive therapy in patients with systemic lupus erythematosus is easy to cause infection, it is also an important cause of patients with multiple organ failure and even death. Long term high dose immunosuppression, corticosteroid therapy, low immunity(low blood leukocyte count,Plasma albumin levels drop), low levels of C3、number of the affected organs, duration of hospitalization, the activity of disease were independent risk factors of infection.2. Bailing Capsule combined with Liuwei Dihuangwan can effectively alleviate the complication that caused by immune inhibitor and hormone in the treatment of systemic lupus erythematosus, and increase clinical therapeutic effect. Besides, it can reduce the risk and the symptoms of infection. Therefore, they aer an effective therapeutic regimen for clinicians in the treatment of systemic lupus erythematosus.3. Bailing Capsule combined with Liuwei Dihuagnwancan increased the secretion of IL-2in patients with systemic lupus erythematosus. This treatment can reduce the infection rate in the systemic lupus erythematosus, it may be associated with increased IL-2that can promote the patients in stable disease. This means they can adjust immune function to improve the lungs, kidneys and other organs function from the side, and can improve the immunity function.Significance1.Technique route of this research is practical and clear. This research mainly observed the effect about the regulation of immune medicine on immunosuppressive therapy in patients with systemic lupus erythematosus complicated with infection. At present the same study rarely seen at home and abroad. The research content is novel and clinical practicability is very strong. This study broaden the research perspective and lay a certain foundation for further research.2.This study examined the level of IL-2in the patients with systemic lupus erythematosus, and found that the increased IL-2of the treatment group is contacted with the reduce of infection in this group. The report provides the basis to investigate the mechanism of regulation of immune medicine through cytokine network. In addition, it also provides a valuable paradigm for evaluation about this kind of drug on the therapeutic effects.