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Wan-Ju Lee, Todd A Lee, Gregory S Calip, Katie J Suda, Leslie Briars, Glen T Schumock
Background: Prior studies evaluating the relationship between tumor necrosis factor-alpha inhibitors (TNFI) and infection were conducted in adults and had conflicting findings. We sought to examine the risk of serious infection associated with TNFIs compared with nonbiologic immunomodulators in children and young adults with inflammatory bowel disease (IBD) and to compare the risk among individual TNFIs. Methods: We conducted a cohort study using the Truven MarketScan Commercial Claims and Encounters database of patients age <30 years with a diagnosis of IBD who initiated treatment with a TNFI or immunomodulator (thiopurines or methotrexate) between 2009 and 2013...
March 19, 2018: Inflammatory Bowel Diseases
Susanna Esposito, Manuel E Soto-Martinez, Wojciech Feleszko, Marcus H Jones, Kun-Ling Shen, Urs B Schaad
PURPOSE OF REVIEW: To provide an overview of the mechanistic and clinical evidence for the use of nonspecific immunomodulators in paediatric respiratory tract infection (RTI) and wheezing/asthma prophylaxis. RECENT FINDINGS: Nonspecific immunomodulators have a long history of empirical use for the prevention of RTIs in vulnerable populations, such as children. The past decade has seen an increase in both the number and quality of studies providing mechanistic and clinical evidence for the prophylactic potential of nonspecific immunomodulators against both respiratory infections and wheezing/asthma in the paediatric population...
March 20, 2018: Current Opinion in Allergy and Clinical Immunology
Ann Joo Lee, Dale F Kraemer, Ozdemir Kanar, Andrew C Berry, Carmen Smotherman, Emely Eid
Background: Inflammatory bowel disease (IBD) can disrupt normal sleep physiology and amplify a negative perception about quality of life. Evidence suggests increased circulation of inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-1, may play a role. Methods: A total of 56 patients completed the Pittsburgh Sleep Quality Index (PSQI) to measure 7 sleep domains: sleep quality, sleep latency, sleep duration, sleep efficacy, sleep disturbance, sleep medications, and daytime dysfunction...
2018: Ochsner Journal
Akhilesh Kumar, Manas Ranjan Dikhit, Ajay Amit, Amir Zaidi, Raj Kishor Pandey, Ashish Kumar Singh, Shashi S Suman, Vahab Ali, Vidya Nand Rabi Das, Krishna Pandey, Vikas Kumar, Shubhankar Kumar Singh, Shyam Narayan, Hirendra Kumar Chourasia, Pradeep Das, Sanjiva Bimal
We report here a Leishmania donovani ornithine decarboxylase (Ld-ODC) gene used as a DNA vaccine against visceral leishmaniasis in a murine Balb/c mouse model. This study also evaluated the possible mechanism of action directed by this candidate. We found a Th1 immune response after immunization using an Ld-ODC DNA vaccine, with results based on the rearrangement of TCR-V-α-2, proliferation of Carboxy fluorescein Succinimidyle ester positive T cells, which were able to produce cytokines such as TNF-α, IFN-γ, IL-12 and IL-2, but not IL-4, IL-5, IL-6 and IL-10, and modulations of the STAT-1 and p38 MAP kinase signaling pathways...
March 17, 2018: Molecular Immunology
Ramsey Hachem, Paul Corris
BACKGROUND: Lung transplantation is a therapeutic option for select patients with end-stage lung disease. However, successful lung transplantation is hampered by chronic lung allograft dysfunction (CLAD), in particular bronchiolitis obliterans syndrome (BOS). Although there is no approved or standard treatment for BOS, which may have several distinct phenotypes, extracorporeal photopheresis (ECP) has shown promising results in patients who develop BOS refractory to azithromycin treatment...
March 19, 2018: Transplantation
Le H Hua, Tracey H Fan, Devon Conway, Nicolas Thompson, Tyler G Kinzy
BACKGROUND: The risk-benefit ratio of continuing immunomodulating disease-modifying therapy (DMT) in older multiple sclerosis (MS) patients is unknown. OBJECTIVE: To evaluate clinical and patient-reported outcomes after stopping DMT in older MS patients. METHODS: Retrospective, observational study identifying patients from our MS clinics who were aged over 60 and on DMT > 2 years. Cause-specific Cox proportional hazards regression modeled time to discontinuation and time to reinitiation of therapy...
March 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Riccardo Marconcini, Francesco Spagnolo, Luigia Stefania Stucci, Simone Ribero, Elena Marra, Francesco De Rosa, Virginia Picasso, Lorenza Di Guardo, Carolina Cimminiello, Stefano Cavalieri, Laura Orgiano, Enrica Tanda, Laura Spano, Alfredo Falcone, Paola Queirolo
Metastatic melanoma was the first malignancy in which immune checkpoint inhibitors demonstrated their successful efficacy. Currently, the knowledge on the interaction between the immune system and malignant disease is steadily increasing and new drugs and therapeutic strategies are overlooking in the clinical scenario. To provide a comprehensive overview of immune modulating drugs currently available in the treatment of melanoma as well as to discuss of possible future strategies in the metastatic melanoma setting, the present review aims at analyzing controversial aspects about the optimal immunomodulating treatment sequences, the search for biomarkers of efficacy of immunocheckpoint inhibitors, and innovative combinations of drugs currently under investigation...
February 23, 2018: Oncotarget
Dong Gao, Yongguang Cai, Yanyuan Chen, Wang Li, Chih-Chang Wei, Xiaoling Luo, Yuhuan Wang
Toll-like receptor (TLR) 7/8 agonists have been applied in combination with chemo-, radio- or immunotherapy for lymphoma, and used as topical drugs for the treatment of viral skin lesions and skin tumors. In the present study, the role of an adenine analog, 9-(4-carboxyphenyl)-8-hydroxy-2-(2-methoxyethoxy)-adenine [termed Gao Dong (GD)], a novel TLR7 agonist, in the activation of cytokine-induced killer/natural killer (CIK/NK) cells was determined. The results of the present study indicated that GD was able to activate CIK/NK cells...
April 2018: Oncology Letters
Katya B Rubinow
BACKGROUND: Over the past two decades, parallel recognition has grown of the importance of both sex steroids and immune activity in metabolic regulation. More recently, these discrete areas have been integrated in studies examining the metabolic effects of sex steroid immunomodulation. Implicit in these studies has been a traditional, endocrine model of sex steroid delivery from the gonads to target cells, including immune cells. Thus, research to date has focused on the metabolic effects of sex steroid receptor signaling in immune cells...
March 8, 2018: Molecular Metabolism
Yolanda Revilla, Daniel Pérez-Núñez, Juergen A Richt
African swine fever (ASF) is an acute and often fatal disease affecting domestic pigs and wild boar, with severe economic consequences for affected countries. ASF is endemic in sub-Saharan Africa and the island of Sardinia, Italy. Since 2007, the virus emerged in the republic of Georgia, and since then spread throughout the Caucasus region and Russia. Outbreaks have also been reported in Belarus, Ukraine, Lithuania, Latvia, Estonia, Romania, Moldova, Czech Republic, and Poland, threatening neighboring West European countries...
2018: Advances in Virus Research
K M Okoniewska, A E Kedzierska, J Okoniewski, A Slawek, K Grzymajlo, A Chelmonska-Soyta, T Grabowski
Epitopes of regulatory T cells (tregitopes) represent linear sequences of amino acids that induce CD4+ CD25+ Foxp3+ T lymphocytes expansion both in vitro and in vivo. The tregitopes' effectiveness was confirmed in autoimmune disease mouse models and in murine transplant models. Therefore, tregitopes together with regulatory T cells (Tregs) could play a major role in maintaining immune tolerance. The purpose of the presented study was a selection of potential tregitopes and assessment of their impact on Tregs expansion...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Dongyan Shi, Tongguan Tian, Shu Yao, Kelei Cao, Xingxing Zhu, Mingshun Zhang, Shuang Wen, Longjun Li, Meiqing Shi, Hong Zhou
Neuropsychiatric (NP) involvement in systemic lupus erythematosus (SLE) severely impacts patients' quality of life and leads to a poor prognosis. The current therapeutic protocol, corticosteroid administration, can also induce neuropsychiatric disorders. FTY720 is an immunomodulator that selectively confines lymphocytes in lymph nodes and reduces autoreactive T cell recruitment to the central nervous system (CNS). This study aimed to identify a novel therapeutic strategy for NPSLE. B6.MRL-lpr mice were treated with oral administration of FTY720 (2 mg/kg) three times per week for 12 weeks, to evaluate its efficacy in a model of NPSLE...
March 13, 2018: Brain, Behavior, and Immunity
Linjie Zhao, Wei Wang, Shuang Huang, Zhengnan Yang, Lian Xu, Qilian Yang, Xiu Zhou, Jinjin Wang, Qiuhong Shen, Chenlu Wang, Xiaobing Le, Min Feng, Nianxin Zhou, Wayne Bond Lau, Bonnie Lau, Shaohua Yao, Tao Yi, Xin Wang, Xia Zhao, Yuquan Wei, Shengtao Zhou
BACKGROUND: Ovarian cancer constitutes one of the most lethal gynecologic malignancies for females. Currently, early detection strategies and therapeutic options for ovarian cancer are far from satisfactory, leading to high diagnosis rates at late stages and disease relapses. New avenues of therapy are needed that target key processes in ovarian cancer progression. While a variety of non-coding RNAs have been proven to regulate ovarian cancer metastatic progression, the functional roles of RNA-binding proteins (RBPs) in this process are less well defined...
March 16, 2018: Genome Biology
Mitsuhiro Akiyama, Tsutomu Takeuchi
IgG4-related disease is a heterogeneous immune-mediated fibroinflammatory condition that can affect every single organ. This disease is more prevalent in the elderly (the mean age of patients is above 60 years) and the prevalence rate is estimated to be over 4.6 per 100,000 population. Before making a diagnosis, the exclusion of malignancies, lymphoma, anti-neutrophil cytoplasmic antibody-associated vasculitis, multicentric Castleman disease, and other mimickers is crucial for appropriate treatment. Broad management guidelines have been published emphasizing the need for prompt treatment and the use of glucocorticoids as first-line drug therapy for induction of remission...
March 15, 2018: Drugs & Aging
Konstantinos H Katsanos, Konstantinos Papamichael, Joseph D Feuerstein, Dimitrios K Christodoulou, Adam S Cheifetz
The pharmacological management of inflammatory bowel disease (IBD) over the last two decades has transitioned from reliance on aminosalycilates, corticosteroids and immunomodulators to earlier treatment with anti-tumor necrosis factor (anti-TNF) therapy. Nevertheless, 20-30% of patients discontinue anti-TNF therapy for primary non-response and another 30-40% for losing response within one year of treatment. These undesirable therapeutic outcomes can be attributed to pharmacokinetic (anti-drug antibodies and/or low drug concentrations) or pharmacodynamic issues characterized by a non-TNF driven inflammation...
March 12, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Ilaria Cavazzana, Laura Andreoli, Maarteen Limper, Franco Franceschini, Angela Tincani
PURPOSE OF REVIEW: This review focuses on new clinical aspects of antiphospholipid syndrome (APS) in the last 5 years. RECENT FINDINGS: The pathogenesis of APS is related to endothelial activation by mechanisms other than autoantibody-mediated massive coagulation. These include Toll-like receptors, the m-TORC pathway, and neutrophil activation, inducing an uncontrolled inflammatory cascade. Given these new pathogenetic hypotheses, the treatment of APS could be directed towards a fine balance between anticoagulation and immunomodulation...
March 15, 2018: Current Rheumatology Reports
Paulino Alvarez, Alexandros Briasoulis
PURPOSE OF REVIEW: Immune system activation plays a central role in heart failure progression. Large-scale immune modulatory clinical trials targeting tumor necrosis factor-α and broad spectrum immune modulation have been negative. The objective of this review is to highlight past, present, and what is in the horizon for the immunomodulation in heart failure with a focus of biologics. RECENT FINDINGS: Strategies targeting interleukin-1 pathway are currently undergoing clinical evaluation and data from pilot studies are promising...
March 15, 2018: Current Treatment Options in Cardiovascular Medicine
Sagus Sampath, Haejung Won, Erminia Massarelli, Min Li, Paul Frankel, Nayana Vora, Lalit Vora, Ellie Maghami, Marcin Kortylewski
Immunomodulation contributes to the antitumor efficacy of the fractionated radiation therapy (RT). Here, we describe immune effects of RT with concurrent systemic cisplatin or cetuximab treatment of patients with stage III-IV head and neck squamous cell carcinoma (HNSCC). Using longitudinally collected blood samples, we identified significant changes in cytokines/chemokines and immune cell populations compared to immune-related gene expression profiles in peripheral blood mononuclear cells (PBMCs). The 7-week combinatorial RT resulted in gradual elevation of proinflammatory mediators (IFNγ, IL-6, TNFɑ, CCL2), while levels of IL-12, cytokine essential for antitumor immune responses, were decreased...
February 16, 2018: Oncotarget
Dimity H Ball, Lamyaa Al-Riyami, William Harnett, Margaret M Harnett
ES-62 is a secreted parasitic worm-derived immunomodulator that exhibits therapeutic potential in allergy by downregulating aberrant MyD88 signalling to normalise the inflammatory phenotype and mast cell responses. IL-33 plays an important role in driving mast cell responses and promoting type-2 allergic inflammation, particularly with respect to asthma, via MyD88-integrated crosstalk amongst the IL-33 receptor (ST2), TLR4 and FcεRI. We have now investigated whether ES-62 targets this pathogenic network by subverting ST2-signalling, specifically by characterising how the functional outcomes of crosstalk amongst ST2, TLR4 and FcεRI are modulated by the worm product in wild type and ST2-deficient mast cells...
March 14, 2018: Scientific Reports
Federica Scaletti, Joseph Hardie, Yi-Wei Lee, David C Luther, Moumita Ray, Vincent M Rotello
The delivery of proteins into cells is a potential game changer for a wide array of therapeutic purposes, including cancer therapy, immunomodulation and treatment of inherited diseases. In this review, we present recently developed nanoassemblies for protein delivery that utilize strategies that range from direct assembly, encapsulation and composite formation. We will discuss factors that affect the efficacy of nanoassemblies for delivery from the perspective of both nanoparticles and proteins. Challenges in the field, particularly achieving effective cytosolar protein delivery through endosomal escape or evasion are discussed...
March 14, 2018: Chemical Society Reviews
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