灵芝多糖对人工感染IBDV雏鸡免疫抑制的调节作用

为了了解灵芝多糖(GLP)对人工感染传染性法氏囊病毒(IBDV)雏鸡淋巴细胞增殖和血清中细胞因子含量的影响,试验选取IBDV抗体阴性雏鸡150只,随机分为6组,每组25只,分别设为GLP高、中、低浓度组及空白对照组、黄芪多糖(APS)组和IBD模型组。18日龄时,除空白对照组外其他各组鸡人工感染IBDV。21日龄时,GLP高浓度组(GLP,40 mg/kg/d)、GLP中浓度组(GLP,20 mg/kg/d)、GLP低浓度组(GLP,10 mg/kg/d)、APS组(APS,10 mg/kg/d)雏鸡灌服给药,连用5 d。20,27,34,41日龄时,MTT比色法测定外周血和脾脏淋巴细胞增殖情况,ELISA试剂盒测定血清中IFN-γ、IL-4和IL-6浓度。结果表明:41日龄时,各浓度GLP均能提高IBDV感染雏鸡外周血淋巴细胞OD490值,其中GLP中、低浓度组显著高于模型组(P<0.05)。与IBD模型组比较,各浓度GLP均能提高IBDV感染雏鸡脾淋巴细胞OD490值,以低浓度组最好;与IBD模型组比较,各浓度GLP均能提高免疫抑制型雏鸡血清中IL-4、IL-6和IFN-γ的浓度,其中以低浓度组效果最好,在34,41日龄时均显著高于IBD模型组(P<0.05)。说明连续经口灌服一定浓度灵芝多糖能有效提高IBDV感染雏鸡的免疫力,以GLP低浓度组效果好。

Effect of Echinacea purpurea Polysaccharide on IL-6 m RNA Expression Level in IEC-6 Cell after LPS Injury

[Objective] The aim was to investigate the effect of Echinacea purpurea polysaccharide （EPS） on IL-6 mRNA expression level in IEC-6 cell after lipopolysac- charide （LPS） injury. [Method] Total RNA of IEC-6 cell was extracted with TRIzon reagent and amplified by R-r-PCR. The amplification products were examined by a- garose gel electrophoresis and graphed for analysis. [Result] After stimulation by LPS, the IL-6 mRNA expression level in iEC-6 cell increased. However, EPS could inhibit this effect, and the inhibitory effect was dose-dependent. At the concentration of 50 μg/ml, EPS could partially inhibit the IL-6 mRNA expression in IEC-6 cell after LPS stimulation; in the concentration range of 100-500 μg/ml, the inhibitory effect of EPS on IL-6 mRNA expression in iEC-6 cell increased with the increase of con- centration. When the IEC-6 cell was pre-treated with EPS （50, 100, 200 and 500 μg/ml） for 24 h and then stimulated with LPS （10 μg/ml） for 1 and 4 h, respectively, it was found that the LPS-induced mRNA expression of IL-6 in IEC-6 cell was in- hibited by EPS, and this kind of inhibitory effect was time-dependent. [Conclusion] After small intestinal epithelial cells were stimulated by LPS, the IL-6 mRNA expres- sion level increased. However, EPS could inhibit the LPS-induced mRNA expression of IL-6, thus protecting the intestinal mucosa. In addition, this kind of inhibitory effect showed time and concentration dependence.

Controversies in the treatment of Crohn’s disease: The case for an accelerated step-up treatment approach

The ideal treatment strategy for Crohn’s disease (CD) remains uncertain, as does the optimal endpoint of therapy. Top-down versus step-up describes two different approaches: early use of immunomodulators and biological agents in the former versus initial treatment with steroids in the latter, with escalation to immunomodulators or biological drugs in patients proven to be steroid refractory or steroid dependent. Top-down therapy has been associated with higher rates of mucosal healing. If mucosal healing proves to be associated with better long-term outcomes, such as a decreased need for hospitalization and surgery, top-down therapy may be the better approach for many patients. The main concern with the top-down approach is the toxicity of the immunomodulators and biological agents, which have been linked with infectious complications as well as an increased risk of lymphoma. It is unlikely that one strategy will be best for all patients given the underlying heterogeneity of CD presentation and severity. Ultimately, we must weigh the safety and efficacy of the therapies with the risks of the disease itself. Unfortunately our ability to risk stratify patients at diagnosis remains rudimentary. The purpose of this paper is to review the data that supports or refutes the differing treatment paradigms in CD, and to provide a rationale for an approach, termed the "accelerated step-up" approach, which attempts to balance the risks and benefits of our currently available therapies with the risk of disease related complications as we understand them in 2008.

Recent advances in cytokines:Therapeutic implications for inflammatory bowel diseases

Inflammatory bowel diseases （IBDs） are complex and chronic disabling conditions resulting from a dysregulated dialogue between intestinal microbiota and components of both the innate and adaptive immune systems. Cytokines are essential mediators between activated immune and non-immune cells, including epithelial and mes- enchymal cells. They are immunomodulatory peptides released by numerous cells and these have significant effects on immune function leading to the differentiation and survival of T cells. The physiology of IBD is becom- ing a very attractive field of research for development of new therapeutic agents. These include cytokines involved in intestinal immune inflammation. This review will focus on mechanisms of action of oytokines involved in IBD and new therapeutic opportunities for these diseases.

Role of genetics in the diagnosis and prognosis of Crohn's disease

Considering epidemiological,genetic and immunological data,we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease.It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation.Several genes have been so far related to the diagnosis of Crohn's disease.Those genes are related to innate pattern recognition receptors,to epithelial barrier homeostasis and maintenance of epithelial barrier integrity,to autophagy and to lymphocyte differentiation.So far,the most strong and replicated associations with Crohn's disease have been done with NOD2,IL23R and ATG16L1 genes.Many genes have so far been implicated in prognosis of Crohn's disease and many attempts have been made to classify genetic profiles in Crohn's disease.CARD15 seems not only a susceptibility gene,but also a disease-modifier gene for Crohn's disease.Enriching our understanding on Crohn's disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians.

Novel approaches towards conquering hepatitis B virus infection

Currently approved treatments for hepatitis B virus （HBV） infection include the immunomodulatory agent, IFN-α, and nucleos（t）ide analogues. Their efficacy is limited by their side effects, as well as the induction of viral mutations that render them less potent. It is thus necessary to develop drugs that target additional viral antigens. Chemicals and biomaterials by unique methods of preventing HBV replication are currently being developed, including novel nucleosides and newly synthesized compounds such as capsid assembling and mRNA transcription inhibitors. Molecular therapies that target different stages of the HBV life cycle will aid current methods to manage chronic hepatitis B （CriB） infection. The use of immunomodulators and gene therapy are also under consideration. This report summarizes the most recent treatment possibilities for CHB infection. Emerging therapies and their potential mechanisms, efficacy, and pitfalls are discussed.

Old-age inflammatory bowel disease onset:A different problem?

Inflammatory bowel disease （IBD） in patients aged 60 accounts for 10%-15% of cases of the disease. Diganostic methods are the same as for other age groups. Care has to be taken to distinguish an IBD colitis from other forms of colitis that can mimick clinically, endoscopically and even histologically the IBD entity. The clinical pattern in ulcerative colitis （UC） is proctitis and left-sided UC, while granulomatous colitis with an inflammatory pattern is more common in Crohn’s disease （CD）. The treatment options are those used in younger patients, but a series of considerations related to potential pharmacological interactions and side effects of the drugs must be taken into account. The safety profile of conventional immunomodulators and biological therapy is acceptable but more data are required on the safety of use of these drugs in the elderly population. Biological therapy has risen question on the possibility of increased side effects, however this needs to be confirmed. Adherence to performing all the test prior to biologic treatment administration is very important. The overall response to treatment is similar in the different patient age groups but elderly patients have fewer recurrences. The number of hospitalizations in patients 65 years is greater than in younger group, accounting for 25% of all admissions for IBD. Mortality is similar in UC and slightly higher in CD, but significantly increased in hospitalized patients. Failure of medicaltreatment continues to be the most common indication for surgery in patients aged 60 years. Age is not considered a contraindication for performing restorative proctocolectomy with an ileal pouch-anal anastomosis. However, incontinence evaluation should be taken into account an individualized options should be considered

Development of artemisinin drugs in the treatment of autoimmune diseases

Artemisinin drugs are a family of sesquiterpene trioxane lactone agents originally derived from Artemisia annua L. Due to the big victory in the antimalarial battle,the 2015 Nobel Prize goes to the discoverer of artemisininbased therapy for malaria. Beyond antimalaria, artemisinin and its derivatives are also being investigated in diseases like schistosomiasis, viral infection, cancers and inflammation. Over the past decades, the anti-inflammatory and immunomodulatory effects of artemisinin drugs have been comprehensively studied. In this article, we will briefly describe the development of artemisinin drugs, especially novel artemisinin derivatives, in the treatment of autoimmune diseases.

Medullary thymic epithelial cells,the indispensable player in central tolerance

Crosstalk between thymocytes and thymic epithelial cells is critical for T cell development and the establishment of central tolerance.Medullary thymic epithelial cells(mTECs) play important roles in the late stage of T cell development,especially negative selection and Treg generation.The function of mTECs is highly dependent on their characteristic features such as ectopic expression of peripheral tissue restricted antigens(TRAs) and their master regulator-autoimmune regulator(Aire),expression of various chemokines and cytokines.In this review,we summarize the current understanding of cellular and molecular mechanisms of mTEC development and its functions in T cell development and the establishment of central tolerance.The open questions in this field are also discussed.Understanding the function and underlying mechanisms of mTECs will contribute to the better control of autoimmune diseases and the improvement of immune reconstitution during aging or after infection,chemotherapy or radiotherapy.