Biological therapy for ulcerative colitis: what is after anti-TNF

Ulcerative Colitis (UC) is an idiopathic chronic inflammation. Its etiology is still largely unknown. Environmental and genetic factors in combination with the microbial flora or specific microorganisms are thought to trigger the gut inflammation, leading to the activation of the intestinal immune response. Immune and non-immune cells create a cross talk via the secretion of soluble mediators and expression of cell adhesion molecules, resulting in further cell activation. Mediators such as cytokines and chemokines play a key role in cell recruitment and polarization, intercellular signal amplification or activation and differentiation. Lack of balance between pro-inflammatory and anti-inflammatory cytokines is crucial in the pathogenesis of IBD. Conventional therapy of UC quite commonly fails to avoid complications or colectomy and the therapeutic armamentarium remains still limited. New therapeutic options, such as, biological therapy, gene therapy, hematopoietic stem cell transplantation, and leucoapheresis, have been investigated recently. Biological therapy is focused on different targets involved in the inflammatory process. Several new biological drugs have been introduced in the last decade or are under investigation for the treatment of IBD. They include anti TNF-α agents, anti adhesion molecules, anti IL-12/23, anti IL-6R and more. We review the recent advances in biological therapy for UC treatment beyond the anti-TNFs.     

Biologic therapy for inflammatory bowel disease

Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. This complex interplay of genetic, microbial and environmental factors culminates in a sustained activation of the mucosal immune and non-immune response, probably facilitated by defects in the intestinal epithelial barrier and mucosal immune system, resulting in active inflammation and tissue destruction. Under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory (tumour necrosis factor [TNF]-alpha, interferon [IFN]-gamma, interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may, therefore, be a logical target for IBD therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, T-helper cell (T(h))-1 polarisation, T-cell activation or nuclear factor (NF)-kappaB, and other miscellaneous therapies are being evaluated as potential therapies for IBD. In this context, infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulising Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP 571, certolizumab pegol (CDP 870), etanercept, onercept and adalimumab. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved in the inflammatory process. Lymphocyte-endothelial interactions mediated by adhesion molecules are important in leukocyte migration and recruitment to sites of inflammation, and selective blockade of these adhesion molecules is a novel and promising strategy to treat Crohn's disease. Therapeutic agents that inhibit leukocyte trafficking include natalizumab, MLN-02 and alicaforsen (ISIS 2302). Other agents being investigated for the treatment of Crohn's disease include inhibitors of T-cell activation, peroxisome proliferator-activated receptors, proinflammatory cytokine receptors and T(h)1 polarisation, and growth hormone and growth factors. Agents being investigated for treatment of ulcerative colitis include many of those mentioned for Crohn's disease. More controlled clinical trials are currently being conducted, exploring the safety and efficacy of old and new biologic agents, and the search certainly will open new and exciting perspectives on the development of therapies for IBD.     

A new target for the treatment of inflammatory bowel disease: Interleukin-37

Interleukin (IL)-37 belongs to the IL-1 cytokine family. It has anti-inflammatory effects on numerous autoimmune diseases such as asthma, psoriasis, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA). Mechanistically, IL-37 plays an anti-inflammatory role by regulating the expression of inflammatory factors in two ways: binding extracellular receptors IL-18R or transferring into the nucleus with Smad3. IBD is a kind of idiopathic intestinal inflammatory disease with unknown etiology and pathogenesis. Recent researches had proved that IL-37 is negatively involved in the pathogenesis and development of IBD. Among various inflammatory diseases, IL-37 has been shown to regulate inflammatory development by acting on various immune cells such as neutrophils, macrophages (Mϕ), dendritic cells (DCs), T cells and intestinal epithelial cells. This review summarizes the biological role of IL-37, and its immunoregulatory effects on the immune cells, especially anti-inflammatory function in both human and experimental models of IBD.     

抗白细胞介素6及其受体单克隆抗体治疗自身免疫病研究进展

白细胞介素6 (interleukin-6,IL-6)是调节免疫反应和炎性反应的多效性细胞因子,通过形成IL-6/IL-6受体(IL-6 receptor,IL-6R)/gp130复合体发挥生物学作用.因此,靶向抑制IL-6或IL-6R的单克隆抗体(单抗)可以用来治疗自身免疫病.随着包括IL-6/IL-6R抑制剂在内的多种生物制剂推向临床,新的问题也开始产生,如选用何种药物既可以改善病情又能避免严重不良反应.此文以抗IL-6单抗Sirukumab和抗IL-6R单抗Tocilizumab为代表,着重对这类药物治疗各种自身免疫病的有效性和安全性进行综述.     

New developments in the treatment of inflammatory bowel disease

Therapy of inflammatory bowel disease (IBD) is rapidly changing with the advent of new discoveries in disease pathogenesis. The need for targeted therapies against the uncontrolled immuno-inflammatory reaction in IBD together with a prerequisite for minimal side effects is driving improvement in old medicines and is leading to the development of new drugs. This review introduces emerging changes in IBD treatment, such as improvements in conventional IBD medications or their use. Balsalazide, budesonide and changes in the use of 5-aminosalicylate (5-ASA) products and purine analogues, such as azathioprine, are discussed. Additionally, studies examining the role of drugs newly introduced into IBD therapy, such as mycophenolate mofetil (MMF), thalidomide and heparin, are stated. Emerging biological therapies, such as therapies against TNF, therapies to enhance anti-inflammatory cytokines, therapeutic manoeuvres to disrupt immune cell trafficking, anti-oxidant therapies, as well as non-conventional treatments, such as diet therapies, prebiotics and probiotics, and helminth therapies are discussed.     

New developments in the treatment of inflammatory bowel disease

Therapy of inflammatory bowel disease (IBD) is rapidly changing with the advent of new discoveries in disease pathogenesis. The need for targeted therapies against the uncontrolled immuno-inflammatory reaction in IBD together with a prerequisite for minimal side effects is driving improvement in old medicines and is leading to the development of new drugs. This review introduces emerging changes in IBD treatment, such as improvements in conventional IBD medications or their use. Balsalazide, budesonide and changes in the use of 5-aminosalicylate (5-ASA) products and purine analogues, such as azathioprine, are discussed. Additionally, studies examining the role of drugs newly introduced into IBD therapy, such as mycophenolate mofetil (MMF), thalidomide and heparin, are stated. Emerging biological therapies, such as therapies against TNF, therapies to enhance anti-inflammatory cytokines, therapeutic manoeuvres to disrupt immune cell trafficking, anti-oxidant therapies, as well as non-conventional treatments, such as diet therapies, prebiotics and probiotics, and helminth therapies are discussed.     

Boosting interleukin-10 production: therapeutic effects and mechanisms

More than forty cytokines have been extensively researched on the molecular structure, cell signaling and transduction pathway. With respect to cytokine-regulating therapy in immunological imbalance however, the reported results are conflicting because of the pleiotropic functions and the intricate interactions of the cytokine network. In this review, we outline the observations on interleukin-10 (IL-10) upregulatory therapy. Despite varying opinions on its therapeutic effects for different disorders, IL-10 has been considered a potential anti-inflammatory cytokine. Numerous studies support the view that IL-10 shows a strong suppressive effect on Th1 lymphocytes, antigen presenting cells and the production of inflammatory mediators. It is also noticeable that recent research has revealed the relationship between IL-10 induced antigen specific regulatory CD4+ T cells and antigen specific immune tolerance. This specific regulation was mediated in part through IL-10 secretion, because anti-IL-10 treatment reverted the inhibitory effect of regulatory T cell clones. In different models, these cells were shown to inhibit both Th1 and Th2-type inflammatory responses through the secretion of IL-10. With the presence of IL-10, regulatory T cells may induce peripheral immune tolerance. Exogenous administration, transgenic expression and endogenous stimulative agents of IL-10 have been used for a variety of inflammatory diseases, autoimmune diseases and allograft rejection in patients and experimental models. A therapeutic intervention with drug inducing endogenous IL-10 may be more practical than an exogenous administration of IL-10 with transient effect. Although further investigation on gene regulation of IL-10 is necessary, increasing studies have been reported concerning the attempt to develop the agents, which could promote endogenous IL-10 production for the treatment of immunological disorders and inflammatory diseases. With some unclear mechanisms, these agents have strongly upregulated IL-10 production in vitro or in vivo. Reported IL-10 upregulatory agents have shown promising prospects for remission of autoimmune diseases and inflammatory diseases and have even induced antigen specific immune tolerance. It is interesting that the IL-10 upregulatory effect of several traditional immunosuppressive drugs has been detected, e.g. glucocorticoid, which is considered "not more as an immunosuppressive drug but an immune modulating agent". Approximately twenty IL-10 upregulatory agents as instances are described in the present review. In addition, their therapeutic effects in various diseases are discussed.     

Understanding the use of immunosuppressive agents in the clinical management of IBD

The advent of the biological era has seen many improvements in the management of inflammatory bowel disease (IBD). These agents, however, are not a ubiquitous panacea as they are neither universally available nor are they universally efficacious in the short or long-term. There is, therefore, still a need for other therapies and it is important to remember about the medications that have been effective in the past. The use of azathioprine and 6-mercoptopurine has been the mainstay of long-term therapy for many IBD patients for many years. Their role as steroid sparing agents and in the maintenance of remission is well recognized, and with the advent of metabolite testing their use has been refined. Methotrexate is a second line immunomodulator with less impressive data but still with observed benefits in Crohn's disease (CD) and two newer immunosuppressive agents, mycophenylate mofetil and tacrolimus have sparked some interest as they appear to be efficacious in some patients. As IBD is a chronic incurable condition that primarily presents in young patients, the treating clinician's goal is to induce and maintain long-term remission. So when one agent is ineffective, or unavailable, other agents need to be considered. This review aims to provide clinicians with practical and up to date knowledge about the use of the immunomodulators in the management of IBD, which is vital in order to offer the best management for their patients.     

Safety and Efficacy of Biologic Agents for the Management of Inflammatory Bowel Disease After Liver Transplantation

Primary sclerosing cholangitis (PSC) frequently progresses to end‐stage liver disease and cirrhosis, requiring liver transplantation. Approximately 70% of patients with PSC have concomitant inflammatory bowel disease (IBD) during their clinical course. After liver transplantation for PSC, corticosteroids and other high‐intensity immunosuppressants are initiated to keep IBD in remission. Patients with IBD that is refractory to these agents may need to be managed with biologic therapies. Biologic agents, however, may further increase the risks for malignancy and infection due to their immunosuppressive effects. Thus, to gain a better understanding of the risks and benefits of these agents in this high‐risk patient population, we performed a literature search of the PubMed database (2002–2017) to identify studies assessing the efficacy and safety of various biologic agents for the management of IBD in liver transplant recipients. No randomized controlled studies or retrospective comparative studies were identified; however, 15 case reports and case series were identified that met our inclusion criteria. From these case reports, we identified 67 patients who developed de novo or recurrent IBD after liver transplantation and received anti–tumor necrosis factor‐α or anti‐integrin therapy. Of the 13 published cases reporting clinical response or remission of IBD activity in liver transplant recipients (59 patients), clinical response or remission of IBD was reported in 38 (64.4%) of those patients. Adverse complications reported included cholangitis, oral candidiasis, Clostridium difficile colitis, bacterial pneumonia, cryptosporidiosis, Epstein–Barr virus–positive posttransplantation lymphoproliferative disease, and hepatotoxicity. Given the limited literature (case reports and case series) highlighted in this review, biologic agents such as tumor necrosis factor‐α inhibitors and integrin inhibitors commonly used for moderate to severe IBD may be appropriate after liver transplantation; however, consideration of risk versus benefit should always occur in a patient‐specific manner.     

Emerging biotherapies for inflammatory bowel disease

The immunological and genetic pathogeneses of inflammatory bowel disease (IBD) have been well studied, but not well elucidated in recent years. Accordingly, the pharmacological treatment of IBD is focusing upon the individual pathologic step (targeting therapy). It has recently become apparent that new drugs such as biological immunomodulating agents and anti-inflammatory cytokines have better short-term effects in some respects than conventional drugs, and they could change the treatment strategy of IBDs in the near future. Many options are now available to treat IBD. The choice depends on the type of IBD, the location of inflammation and the severity of symptoms. Many key processes in the inflammatory cascade have been targeted by cytokine and anticytokine therapies ranging from antigen presentation, T cell activation, overproduction of pro-inflammatory cytokines and migration of inflammatory cells to blockade of effector signals. TNF-alpha plays an important role in the induction of other cytokines as well as in the upregulation of adhesion molecules in chronic IBDs, Crohn's disease (CD) and ulcerative colitis. In fact, the most successful approaches so far in the treatment of IBD have been anti-TNF strategies. In contrast, the use of antiadhesion molecules strategies has been demonstrated to be ineffective in IBD.     

Emerging biotherapies for inflammatory bowel disease

The immunological and genetic pathogeneses of inflammatory bowel disease (IBD) have been well studied, but not well elucidated in recent years. Accordingly, the pharmacological treatment of IBD is focusing upon the individual pathologic step (targeting therapy). It has recently become apparent that new drugs such as biological immunomodulating agents and anti-inflammatory cytokines have better short-term effects in some respects than conventional drugs, and they could change the treatment strategy of IBDs in the near future. Many options are now available to treat IBD. The choice depends on the type of IBD, the location of inflammation and the severity of symptoms. Many key processes in the inflammatory cascade have been targeted by cytokine and anticytokine therapies ranging from antigen presentation, T cell activation, overproduction of pro-inflammatory cytokines and migration of inflammatory cells to blockade of effector signals. TNF-α plays an important role in the induction of other cytokines as well as in the upregulation of adhesion molecules in chronic IBDs, Crohn’s disease (CD) and ulcerative colitis. In fact, the most successful approaches so far in the treatment of IBD have been anti-TNF strategies. In contrast, the use of antiadhesion molecules strategies has been demonstrated to be ineffective in IBD.     

Review article: the role of non-biological drugs in refractory inflammatory bowel disease

Background Up to one‐third of patients with inflammatory bowel disease (IBD) do not respond to, or are intolerant of conventional immunosuppressive drugs. Although biological agents are alternative treatments, they may not be suitable or available to some patients. Aim To review the evidence for use of nonbiological drugs in the treatment of patients with IBD refractory to corticosteroids or thiopurines. Methods A literature search was performed using PubMed for English language publications with predetermined search criteria to identify relevant studies. Results Published evidence from uncontrolled series and controlled clinical trials has been used to produce a practical approach relevant to clinical practice which incorporates the indication, optimal dose, and side effects of various therapies including tacrolimus, methotrexate, thalidomide, tioguanine, mycophenolate mofotil, leucocyte apheresis, nutritional therapy, antibiotics, probiotics, allopurinol, rectal acetarsol and ciclosporin in the treatment of patients with refractory ulcerative colitis and Crohn’s disease. Approaches to optimise thiopurine efficacy are also discussed. Conclusions Patients with IBD refractory to corticosteroids or thiopurines may respond to alternative anti‐inflammatory chemical molecules, but the evidence base for many of these alternatives is limited and further trials are needed.     

Novel approaches to inflammatory bowel disease

Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel disease (IBD), are chronic, spontaneously relapsing disorders of unknown cause. These diseases appear to be immunologically mediated and have genetic and environmental influences. Although the cause of these diseases remains obscure, the pathogenesis of chronic intestinal inflammation is becoming clearer, due to improved animal models of enterocolitis and important advances in immunological techniques. Traditional therapy for IBD, although helping to induce and maintain disease remission, does little to alter the underlying fundamental disease process. New IBD therapy has not developed significantly over the past twenty years and includes 5-aminosalicylic acid preparations, corticosteroids and immunomodulatory agents, such as azathioprine, 6-mercaptopurine and methotrexate. There is, therefore, a need for new, specific disease-modifying therapy and the development of such therapy has been hastened by a greater understanding of the pathophysiology of IBD. This review examines the most recent novel therapies for IBD, with specific emphasis on immunomodulatory and novel anti-inflammatory therapies. Recent clinical trials are reviewed, and the potential advances and clinical impact that these novel agents may provide are discussed.     

Development and validation of a novel IL-10 deficient cell transfer model for colitis

A number of rodent models for inflammatory bowel disease (IBD) have been developed, but most cannot be used to develop and validate new therapies for IBD. From the models developed, the IL-10 deficient mouse model is the one that results in a disease similar to human IBD; however, in this model, colitis occurs with variable incidence taking 3-4 months to develop. These are serious problems with the model when evaluating a new therapy because of the large-scale experiments required and the difficulty in performing an accurate pharmacological analysis. In this study, the IL-10 deficient mouse model was modified by transferring whole spleen and mesenteric lymph node cells from IL-10 deficient mice to CB-17 SCID mice. In this IL-10 deficient cell transfer model, chronic intestinal inflammation developed in all recipients within 2-3 weeks, which was far earlier than in donor IL-10 deficient mice. The pathological phenotypes were similar to those of IL-10 deficient mice and CD45RBhi T cell-transfer models. In addition, we assessed several agents for inflammatory bowel disease to validate the general utility of this cell transfer model. It is worth noting that TNFR-Ig or prednisolone, which is effective for treatment of patients with severe-fulminant Crohn's disease, markedly attenuated pathological clinical indices in this colitis model, whereas the immunosuppressive agents, azathioprine, tacrolimus, and cyclosporine A produced no significant effect. These results suggest that the IL-10 deficient cell transfer model is a good experimental model to use for developing new and effective therapies for active IBD.     

Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives.

Mechanisms underlying the gastric toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) have been extensively investigated, whereas those leading to intestinal damage are not completely understood. Several hypotheses have been put forward on the pathophysiology of intestinal damage by NSAIDs: enhanced intestinal permeability, inhibition of cyclooxygenase (COX), enterohepatic recirculation, and formation of adducts. The effects of COX-2 selective inhibitors, which appear to have better gastric tolerability when compared to nonselective NSAIDs, on normal and inflamed intestinal mucosa (as in Crohn's disease or ulcerative colitis) are still largely unexplored. If COX-2 inhibition plays a key role in suppressing the inflammatory process, recent evidence suggests that COX-2 products are involved in maintaining the integrity of intestinal mucosa, in the healing of gastrointestinal ulcers and in the modulation of inflammatory bowel disease (IBD). Animal models of intestinal inflammation have so far yielded conflicting results on the effects of COX-2 selective inhibitors on the intestinal mucosa. It is now clear that NSAIDs do not act through cyclooxygenase inhibition, but also have different targets such as nuclear factor-kappaB and/or peroxisome proliferator-activated receptors gamma. The peculiar pharmacological profile of each compound may help to explain the different impact of each NSAID on the inflammatory process and on IBD. Notably, the salicylic acid derivative 5-ASA is widely used in the treatment of IBD and is believed to act through nuclear factor-kappaB inhibition. Although the use of COX-2 selective inhibitors remains contraindicated in patients with IBD, studying their effects on intestinal mucosa may offer new insights into their subcellulars mechanisms of action and open new avenues for the development of novel therapies for IBD.     

New insights into the biological therapy of Crohn’s disease

Conventional treatment of Crohn’s disease (CD) has resulted in only a limited therapeutic benefit. Advancing knowledge of CD pathogenesis and recent advances in biotechnology have led to the development of biological agents that selectively target individual inflammatory pathways. Such agents may be divided in anti-TNF-α strategies, lymphocyte trafficking inhibitors, anti-inflammatory cytokines and pro-inflammatory cytokine inhibitors. Based on the early success of infliximab, humanised anti-TNF-α antibodies (CDP-571, CDP-870, adalimumab), soluble TNF-α receptors (etanercept, onercept), mitogen-activated protein kinase (MAPK) inhibitors and NF-κB inhibitors have been developed. To block lymphocyte migration, anti-integrin antibodies (natalizumab, MLN-02), antisense intercellular adhesion molecule-1, antinectin antibodies and chemotactic factors inhibitors have been engineered. Anti-inflammatory cytokines (IL-10, IL-11) have been tested with limited results in Crohn’s disease, but further improvement in delivery of these molecules has been achieved. Pro-inflammatory cytokine inhibitors, such as anti-IL-6 and anti-IL-12, have been shown to be effective in clinical trials; and new antibodies, as well as genetic manipulation, have been developed. The aim of this review is to provide an insight into the biological therapies already applied in human studies, and to the new patents potentially applicable in the forthcom-ing years.     

Targeted anti-IL-13 therapies in asthma: current data and future perspectives

Introduction: The identification of patients with severe asthma who will benefit from a personalized management approach remains an unmet need. Interleukin-13 (IL-13) is a cytokine possessing a significant role in asthma pathogenesis and progression of disease. Humanised monoclonal antibodies against IL-13 and IL-13 and IL-4 receptors are mainly proposed as add-on therapy in patients with T_H2-high inflammation with uncontrolled asthma despite maximum therapy.

Areas covered: The role of IL-13 in airway inflammation in severe asthma, the targeted anti-IL-13 therapies and biomarkers that predict response to anti-IL-13 treatment are discussed.

Expert opinion: New effective individualized therapies in severe asthma are urgently needed to block specific inflammatory pathways using monoclonal antibodies. Studies on anti-IL-13 therapies showed that asthmatic patients could benefit from this novel targeted therapy as far as lung function and exacerbation rate are concerned. T_H2-high and especially periostin-high groups of asthmatics with moderate-to-severe uncontrolled asthma seem to compose the group that could benefit from anti-IL-13 therapy. Targeting IL-13 alone may not be sufficient to achieve asthma control. Inhibition of IL-13 and IL-4 with mabs may be more encouraging and patients will probably have additional benefits from these therapeutic interventions because of IL-13/IL-4 overlapping actions in asthma pathophysiology.     

Cytokines in colitis associated cancer: potential drug targets?

In inflammatory bowel disease (IBD), such as UC and CD, the development of colorectal carcinoma can be initiated through chronic inflammation, depending on the duration and severity of the disease. Growing evidence supports a role for various cytokines, released by epithelial and immune cells, in the pathogenesis of colitis associated cancer (CAC). For instance, TNF-alpha has been recently shown to promote tumor development in experimental colitis. Due to its role in the pathogenesis of IBD, TNF-alpha blockade has become one of the cornerstones of IBD therapy. Thus, anti-TNF-alpha strategies could also provide effective anti-tumor therapies. TGF-beta has been shown to attenuate an anti-tumor immune-response through the induction of regulatory T cells in spontaneous and inflammation associated cancer. However, IL-6 signaling promotes tumor growth in experimental CAC, and this signaling is inhibited by TGF-beta. Members of the IL-12 family, such as IL-12, IL-23, and IL-27, have been implicated in pathogenesis of colitis and IL-23 seems to be involved in inflammation associated carcinogenesis. However, a role for those cytokines in CAC remains to be shown. Whereas the above-mentioned cytokines promote tumor growth, others provide an anti tumor effect. IL-10 deficient mice develop colitis and CAC a few weeks after birth. Besides its immunosuppressive properties, IL-10 also has anti angiogenic and both tumor promoting and -inhibiting properties, which could be responsible for these observations. Since most of the above mentioned cytokines are involved in both, inflammation and carcinogenesis, it is difficult to account their contribution to the individual steps during pathogenesis of CAC. However, as already shown in IBD, cytokines may also provide promising therapeutic targets in CAC.     

肠道菌群在炎症性肠病发病机制与治疗中的作用研究进展

炎症性肠病是一种以肠道炎症和黏膜损伤为特征的慢性疾病,主要包括克罗恩病和溃疡性结肠炎,其发病原因尚不明确。现有研究表明炎症性肠病的发病机制与宿主的遗传易感性、肠道菌群紊乱、肠黏膜屏障破坏和肠黏膜免疫异常等密切相关。总结目前炎症性肠病发病机制、患者肠道菌群结构及治疗方法等相关的研究进展,旨在对今后炎症性肠病的治疗和药物研发有所裨益。     

Anti-inflammatory peptides and proteins in inflammatory bowel disease

Current therapy of inflammatory bowel disease, ie, ulcerative colitis and Crohn's disease, is neither sufficient nor disease-modifying. Long-term treatment with non-specific antiinflammatory drugs aminosalicylates, corticosteroids and immunosuppressants is often accompanied with undesirable and potentially serious side effects. Novel biologically-driven therapies are targeted to specific pathophysiological processes, offering the potential for better treatment outcomes. Among other antiinflammatory peptides and proteins, monoclonal antibodies directed against TNFalpha and adhesion molecule alpha4beta7 integrin, recombinant anti-inflammatory cytokines IL-10 and IL-11, as well as colony-stimulating factors and peptide growth factors, are in the most advanced stages of clinical development for IBD.