Immunomodulatory drugs

免疫调节药物
  • 文章类型: Journal Article
    牛磺酸,由半胱氨酸产生的非必需氨基酸,在身体组织和血浆中含量丰富。它在成长中起着至关重要的作用,渗透,脂质代谢,和神经激素调节。牛磺酸有抗氧化剂,抗凋亡,和抗炎特性,它的缺乏会导致各种疾病,包括心血管疾病,糖尿病,肾,和肝脏疾病。本报告全面综述了牛磺酸在抵消药物诱导的副作用方面的功能特性。跨数据库搜索,如Scopus,PubMed,MEDLINE,WebofScience发表了109篇文章,其中75人被纳入研究。这些结果表明,牛磺酸的保护作用涉及诸如影响Nrf2/OH-1,PI3激酶/AKT和ERK2途径,增强抗氧化剂(SOD,GPx和CAT),和抑制炎症细胞因子(TNF-α,IL-1β和IL-6)。总的来说,补充牛磺酸以及具有明显副作用的药物可以减轻这些影响并增强其功效。对牛磺酸与其他营养素或化合物之间的相互作用的进一步研究可以提供对协同效应和新的治疗方法的见解。
    Taurine, a non-essential amino acid produced from cysteine, is abundant in body tissues and blood plasma. It plays vital roles in growth, osmosis, lipid metabolism, and neurohormonal modulation. Taurine has antioxidant, anti-apoptotic, and anti-inflammatory properties, and its deficiency can lead to various diseases including cardiovascular, diabetic, renal, and liver disorders. This report provides a comprehensive review of the functional properties of taurine in counteracting pharmaceutical-induced side effects. A search across databases such as Scopus, PubMed, MEDLINE, and Web of Science yielded 109 articles, of which 75 were included in the study. These results suggest that the protective effects of taurine involve mechanisms such as influencing pathways of Nrf2/OH-1, PI3-kinase/AKT and ERK2, boosting antioxidants (SOD, GPx and CAT), and suppression of inflammatory cytokines (TNF-α, IL-1β and IL-6). Overall, supplementation with taurine along with medications with significant side effects may mitigate these effects and enhance their efficacy. Further investigation of the interactions between taurine and other nutrients or compounds may provide insights into synergistic effects and novel therapeutic approaches.
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  • 文章类型: Systematic Review
    宿主免疫应答的失调在脓毒症的病理生理学中具有中心作用。免疫调节药物作为败血症的潜在治疗辅助药物已经引起了极大的兴趣。我们对随机对照试验进行了系统评价和荟萃分析,评价免疫调节药物作为标准治疗辅助治疗成人脓毒症的安全性和临床有效性。我们的主要结果是严重不良事件和全因死亡率。五十六个独特的,确定了合格的随机对照试验,评估一系列干预措施,包括细胞因子抑制剂;抗炎药;免疫细胞刺激剂;血小板途径抑制剂和补体抑制剂。在1个月的随访中,使用细胞因子抑制剂与严重不良事件风险降低相关,根据涉及7138例患者的11项研究(RR(95CI)0.95(0.90-1.00),I2=0%)。唯一与严重不良事件风险增加相关的免疫调节药物是toll样受体4拮抗剂(RR(95CI)1.18(1.04-1.34),I2=0%(两次试验,567名患者))。根据18项随机对照试验,涉及11075名患者,细胞因子抑制剂降低了1个月死亡率(RR(95CI)0.88(0.78-0.98),I2=57%)。在评估抗肿瘤坏死因子α干预措施的13项随机对照试验的亚组中也显示出死亡率降低(RR(95CI)0.93(0.87-0.99),I2=0%)。任何剂量的抗炎药在2个月时对死亡率的明显影响最大(两项试验,228名患者,RR(95CI)0.64(0.51-0.80),I2=0%)和3个月的任何剂量(涉及277名患者的三项试验,RR(95CI)0.67(0.55-0.81),I2=0%)。这些数据表明,除了toll样受体4拮抗剂,没有证据表明在脓毒症中使用免疫调节药物存在安全性问题,他们可能显示某些药物的短期死亡率获益。
    Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90-1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04-1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78-0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87-0.99), I2 = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51-0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55-0.81), I2 = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs.
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  • 文章类型: Journal Article
    目前多发性骨髓瘤(MM)的治疗策略已得到改善,由于有效的药物类别和联合疗法,对于前期和复发设置。新诊断的移植不合格患者的临床试验导致免疫调节药物(IMiDs)和蛋白酶体抑制剂(PIs)与抗CD38单克隆抗体(mAb)联合使用,在移植前的诱导阶段和维持治疗期间施用,建议使用来那度胺直至复发。在复发/难治性患者中,复杂的治疗方案目前包括几种选择,例如具有抗CD38单克隆抗体加上IMiD或PI的三胞胎,和新的靶向分子。临床试验和真实世界数据之间的比较表明,一些重要结果具有良好的可重复性,特别是在总体反应率方面,无进展生存期,和总体生存率。这可能有助于临床医生正确选择最佳治疗方案,特别是在现实世界中。然而,与现实环境的管理相比,临床试验在结局方面存在一些缺陷,尤其是在安全性和生活质量方面.事实上,试验包括年轻和可能更健康的患者,排除由于MM特征而具有最差临床状况的患者(例如,肾功能不全或骨骼疾病,这可能会损害性能状态)和合并症(例如,心脏和肺部疾病),因此导致纳入患者的数据可能缺乏代表性.在这次审查中,我们分析临床试验与临床试验的可比和差异结果在过去10年中发布的真实世界设置,重点介绍治疗MM的不同药物和组合,并提供治疗选择的概述。
    The current strategies for the treatment of multiple myeloma (MM) have improved, thanks to effective drug classes and combination therapies, for both the upfront and relapsed settings. Clinical trials for newly diagnosed transplant-ineligible patients led to the approval of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) in combination with anti-CD38 monoclonal antibodies (mAbs), to be administered during the induction phase before transplantation and during maintenance treatment, with lenalidomide recommended until relapse. In relapsed/refractory patients, the complex treatment scenario currently includes several options, such as triplets with anti-CD38 mAbs plus IMiDs or PIs, and novel targeted molecules. Comparisons among clinical trials and real-world data showed a good degree of reproducibility of some important results, particularly in terms of overall response rate, progression-free survival, and overall survival. This may help clinicians towards a proper selection of the best treatment options, particularly in real-world settings. However, as compared with the management of real-world settings, clinical trials have some pitfalls in terms of outcome and especially in terms of safety and quality of life. In fact, trials include younger and presumably healthier patients, excluding those with worst clinical conditions due to MM features (e.g., renal insufficiency or bone disease, which can impair the performance status) and comorbidities (e.g., cardiac and pulmonary disease), thus resulting in a possible lack of representativeness of data about the patients enrolled. In this review, we analyze comparable and discrepant results from clinical trials vs. real-world settings published in the last 10 years, focusing on different drugs and combinations for the treatment of MM and providing an overview of treatment choices.
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  • 文章类型: Journal Article
    Children with autoimmune disorders are especially at risk of vaccine-preventable diseases due to their underlying disease and the immunosuppressive treatment often required for a long period. In addition, vaccine coverage remains too low in this vulnerable population. This can be explained by a fear of possible adverse effects of vaccines under immunosuppression, but also a lack of data and clear recommendations, particularly with regard to vaccination with live vaccines. In this review, the latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to provide a set of practical guidelines on vaccination for specialists caring for children suffering from different autoimmune disorders and treated with various immunosuppressive regimens.
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  • 文章类型: Journal Article
    最近爆发的COVID-19归因于严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)。这种病毒性疾病正在全球范围内迅速蔓延,包括印度。控制这种疾病的主体是支持性治疗,营养,并在没有经过证实的抗病毒药物的情况下阻止进一步的进展。目前,在印度使用了两种疫苗Covishield和Covaxin。开发最可靠的基于mRNA的疫苗的长期计划也正在进行中,以用于未来的预防方法。Siddha医学系统的整体方法强调生活方式的改变,预防性干预措施,和饮食管理,以提高宿主的免疫力,并根据情况使用草药和高级药物进行治疗。在这次审查中,疾病COVID-19,冠状病毒,以证据为基础的传统Siddha干预呼吸系统疾病和免疫增强剂强调了有关个别草药的相关已发表的研究,这为进一步研究COVID-19的药物再利用铺平了道路。研究了Siddha经典中预防和治疗感染特别是抗病毒药物的历史证据。
    The recent outbreak of COVID-19 is attributed to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This viral disease is rapidly spreading across the globe, including India. The mainstay in managing the disease is supportive care, nutrition, and preventing further progression in the absence of proven antiviral drugs. Currently two vaccines Covishield and Covaxin are administered in India. Long-term plans of developing most reliable mRNA-based vaccines are also underway for the future method of prophylaxis. The Siddha system of medicine\'s holistic approach emphasizes lifestyle modification, prophylactic interventions, and dietary management to boost the host immunity and treatment with herbal medicines and higher-order medicines as the case may be. In this review, a brief outline of the disease COVID-19, Coronavirus, evidence-based traditional Siddha interventions for respiratory ailments and immune boosters highlighting the relevant published research on individual herbs are dealt, which pave way for further research on drug repurposing for COVID-19. Historical evidence on the prevention and treatment of infections especially antivirals in Siddha classics is studied.
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  • 文章类型: Journal Article
    2019年冠状病毒病(COVID-19),由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起,是本世纪的严重流行病。该疾病的恶性触角已在世界范围内传播,并产生未知的并发症和影响。晚期COVID-19综合征的特征是促炎细胞因子的释放不受控制和升高,免疫力受到抑制,导致细胞因子风暴。炎性和促炎细胞因子的不受控制和失调的分泌与病毒感染的严重程度和死亡率呈正相关。分泌各种促炎细胞因子如TNF-α,IL-1和IL-6通过招募巨噬细胞导致高炎症反应,肺泡细胞中的T细胞和B细胞。此外,据推测,巨噬细胞等免疫细胞在肺泡细胞中募集炎性单核细胞,并允许肺泡中产生大量细胞因子,导致重症COVID-19患者的高炎症反应。这一系列事件可能导致多器官衰竭,急性呼吸窘迫,或者肺炎。虽然这种疾病比其他慢性疾病有更高的存活率,老年人群的并发症发生率相当高,更多的全身性并发症。本文综述了各种炎症标志物在COVID-19相关并发症中的关键作用。不同的分子途径,例如JAK和JAK/STAT信号的激活在细胞因子风暴的进展中至关重要;因此,各种机制,免疫学途径,以及细胞因子和其他炎症标志物的功能已经被讨论。对细胞因子分子途径及其激活程序的透彻了解将增加对免疫病理学理解和设计适当药物的更多见解。疗法,以及应对COVID-19的控制措施。最近,据报道,抗炎药和几种抗病毒药物是控制高细胞因子血症或细胞因子风暴的有效治疗药物.因此,本综述还讨论了目前处于不同试验阶段的前瞻性抗炎和相关免疫调节药物及其可能的影响.
    Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines\' molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.
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  • 文章类型: Journal Article
    结核病(TB)仍然是全球卫生紧急情况,估计全世界有20亿人被感染,每年有140万人死于这种疾病。病原体的许多方面,结核分枝杆菌,使医疗保健和实验室研究人员难以对抗这种疾病,如独特的病理生理学,潜伏感染和长期复杂的治疗方案,从而导致患者不遵守治疗。新药的开发对于解决这些问题至关重要。重新使用药物是产生有效药物治疗同时规避常规药物开发的许多挑战的有前途的策略。在这方面,在标准治疗方案中加入免疫调节药物以增强一线药物被发现非常有吸引力.不同化学类别和药物类别的药物越来越被证明具有抗结核活性,在体外和体内。本文探讨并讨论了在抗结核病辅助治疗中被重新利用的分子实体,旨在提供其进展的最新情况。
    Tuberculosis (TB) remains a global health emergency, with an estimated 2 billion people infected across the world, and 1.4 million people dying to this disease every year. Many aspects of the causative agent, Mycobacterium tuberculosis, make this disease difficult for healthcare and laboratory researchers to fight against, such as unique pathophysiology, latent infection and long and complex treatment regimens, thus causing patient non-compliance with the treatment. Development of new drugs is critical for tackling these problems. Repurposing drugs is a promising strategy for generating an effective drug treatment whilst circumventing many of the challenges of conventional drug development. In this regard, the incorporation of immunomodulatory drugs into the standard regimen to potentiate frontline drugs is found to be highly appealing. Drugs of diverse chemical classes and drug categories are increasingly being evidenced to possess antitubercular activity, both in vitro and in vivo. This article explores and discusses the molecular entities that have shown promise in being repurposed for use in anti-TB adjunctive therapy and aims to provide the most up-to-date picture of their progress.
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  • 文章类型: Case Reports
    Hidradenitis suppurativa/acne inversa (HS/AI) is one of the most debilitating dermatoses with a strong negative impact on every dimension of quality of life. Treatment is dependent on the severity of clinical manifestations and comorbidities. While anti-inflammatory and antimicrobial approaches are recommended for mild and moderate stages, immunomodulatory drugs have gained increasing interest in all stages of HS/AI. We reviewed the available data on this subject in a narrative review and included not only substances with published final outcome but those where either the ongoing trials or experience from case report. Furthermore, we investigated combined surgical therapy and immunomodulatory drugs and raised specific questions to be answered in controlled settings. This aspect seems to be underrepresented. The first approved medical treatment for HS/AI is adalimumab. Other cytokine, interleukin, Janus kinase and C5a inhibitors and antagonists are under investigation. IL-1 inhibitors and antagonists may become an option for mild to moderate HS/AI, while most of the other medical compounds target moderate to severe HS/AI. Despite medical efforts with immunomodulatory agents, surgery remains a cornerstone of efficient HS/AI therapy. Better outcome in advanced disease might be achieved by combining drug therapy and surgery, but more systematic clinical trials are necessary for the optimal combination.
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  • 文章类型: Case Reports
    UNASSIGNED: Uveal melanoma is a rare tumour caused by genetic factors and alterations in the immune response. Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disorder characterized by an inappropriate or excessive immune response. The two main types of IBD are Crohn\'s disease (CD) and ulcerative colitis (UC). A diagnosis of IBD and the use of immunosuppressive drugs are both independently associated with an increased risk of developing skin melanoma. The association between IBD and uveal melanoma (UM) has not been previously described.
    UNASSIGNED: Two young Caucasian men, aged 24 and 28, developed UM 3 and 15 years, respectively, after being diagnosed with IBD. Both received long-term treatment with immunomodulatory drugs, with periodic switching among the drugs due to the refractory nature of IBD. In both cases, melanoma was treated by brachytherapy with iodine-125 COMS plaque implant at a dose of 75 Gy.
    UNASSIGNED: Chronic inflammation can promote cell proliferation and growth. The use of immunomodulatory drugs is associated with an increased risk of developing melanoma and non-melanoma skin cancer. The two patients described in this report both had long-standing IBD treated with immunomodulatory drugs. It seems reasonable to suggest that these two factors may have promoted the development of uveal melanoma. More studies are warranted to investigate and confirm this possible association.
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  • 文章类型: Journal Article
    美国食品和药物管理局批准沙利度胺及其类似物用于治疗结节性红斑,尽管上世纪中叶有严重出生缺陷的报道。作为免疫调节药物,沙利度胺及其类似物已用于有效治疗各种疾病。在本次审查中,关于沙利度胺及其类似物对免疫系统的影响的临床前数据被整合,包括细胞因子对转分化的影响,抗炎作用,免疫细胞功能调节和血管生成。本综述还调查了沙利度胺作为治疗特发性肺纤维化的治疗选择的最新进展。皮肤纤维化,和眼病。
    The US Food and Drug Administration approved thalidomide and its analogues for the treatment of erythema nodosum leprosum, in spite of the notoriety of reports of severe birth defects in the middle of the last century. As immunomodulatory drugs, thalidomide and its analogues have been used to effectively treat various diseases. In the present review, preclinical data about the effects of thalidomide and its analogues on the immune system are integrated, including the effects of cytokines on transdifferentiation, the anti-inflammatory effect, immune cell function regulation and angiogenesis. The present review also investigates the latest developments of thalidomide as a therapeutic option for the treatment of idiopathic pulmonary fibrosis, skin fibrosis, and ophthalmopathies.
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