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Anti- cytokine therapies

Clémence Granier, Alain Gey, Charles Dariane, Arnaud Mejean, Marc-Olivier Timsit, Charlotte Blanc, Virginie Verkarre, Camélia Radulescu, Elisabeth Fabre, Yann Vano, Stéphane Oudard, Cécile Badoual, Éric Tartour
T cells harboring multiple co-inhibitory molecules lose their anti-tumoral functionality. PD-1 is a clinically approved target in cancer therapy, but its expression alone does not mean dysfunctionality. The expression of Tim-3 on numerous cell types (T cell, Treg, dendritic cell, myeloid cells) favors tumor escape to immune cells. Within many tumors, PD-1/Tim-3 coexpressing CD8-T cells lose their ability to secrete cytokines (IFNγ, IL-2, TNFα) and their intratumoral infiltration correlates with a bad prognosis...
March 2018: Médecine Sciences: M/S
Mei Jiang, Xinghui Liu, Denghai Zhang, Ying Wang, Xiaoxia Hu, Fengxia Xu, Mingming Jin, Fanfan Cao, Limin Xu
BACKGROUND: Acute ischemic stroke (AIS) is the most common type of cerebrovascular disease and is a leading cause of disability and death worldwide. Recently, a study suggested that transformation of microglia from the pro-inflammatory M1 state to the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. Celastrol, a traditional oriental medicine, may have anti-inflammatory and neuroprotective effects. However, the underlying mechanisms remain unknown...
March 14, 2018: Journal of Neuroinflammation
Aleksandra Klimczak, Urszula Kozlowska, Maciej Kurpisz
Muscular dystrophies represent a group of diseases which may develop in several forms, and severity of the disease is usually associated with gene mutations. In skeletal muscle regeneration and in muscular dystrophies, both innate and adaptive immune responses are involved. The regenerative potential of mesenchymal stem/stromal cells (MSCs) of bone marrow origin was confirmed by the ability to differentiate into diverse tissues and by their immunomodulatory and anti-inflammatory properties by secretion of a variety of growth factors and anti-inflammatory cytokines...
March 13, 2018: Archivum Immunologiae et Therapiae Experimentalis
Laura Aragoneses-Fenoll, Gloria Ojeda, María Montes-Casado, Yeny Acosta-Ampudia, Umberto Dianzani, Pilar Portolés, José M Rojo
Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110α conditionally deleted in CD4+ and CD8+ T lymphocytes (p110α-/- ΔT) were used. p110α-/- ΔT mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen...
2018: Frontiers in Immunology
Kevin C Kemp, Kelly Hares, Juliana Redondo, Amelia J Cook, Harry R Haynes, Bronwen R Burton, Mark A Pook, Claire M Rice, Neil J Scolding, Alastair Wilkins
OBJECTIVES: Friedreich's ataxia is an incurable inherited neurological disease caused by frataxin deficiency. Here we report the neuro-reparative effects of myeloablative allogeneic bone marrow transplantation in a humanised murine model of the disease. METHODS: Mice received a transplant of fluorescently-tagged sex mis-matched bone marrow cells expressing wild-type frataxin and were assessed at monthly intervals using a range of behavioural motor performance tests...
March 13, 2018: Annals of Neurology
A Wollenberg, R Fölster-Holst, M Saint Aroman, F Sampogna, C Vestergaard
Atopic dermatitis (AD) is a common, highly pruritic, chronic inflammatory skin disease. Dysfunction of the epidermal barrier is witnessed by an increased transepidermal water loss in lesional and non-lesional AD skin. The inflammation in lesional AD skin is well characterized. Non-lesional skin of AD patients shows histological signs of a subclinical inflammation and a pro-inflammatory cytokine milieu. This microinflammation is present even in seemingly healed skin and must be taken into account regarding treatment of AD...
April 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Wensheng Zhang, Wanzhuo He, Xiaodong Shi, Xiao Li, Yuanyuan Wang, Minghua Hu, Fangli Ma, Ning Tao, Guiqin Wang, Zhihai Qin
Despite decades of research, malignant tumors are extremely difficult to eliminate with conventional methods. Although surgical resection potentially eradicates the problem, only a few cases are suitable for operation, and other approaches often involve harmful consequences. Revolutionary methods are desperately needed to improve patient outcomes and diminish harmful side effects. Myeloid-derived suppressor cells (MDSCs), downregulators of the innate and adaptive immune systems, have been widely studied over the past 2 decades...
March 13, 2018: Phytotherapy Research: PTR
Fionnuala B Hickey, Finian Martin
PURPOSE OF REVIEW: The purpose of this review is to examine the proposed role of immune modulation in the development and progression of diabetic kidney disease (DKD). RECENT FINDINGS: Diabetic kidney disease has not historically been considered an immune-mediated disease; however, increasing evidence is emerging in support of an immune role in its pathophysiology. Both systemic and local renal inflammation have been associated with DKD. Infiltration of immune cells, predominantly macrophages, into the kidney has been reported in a number of both experimental and clinical studies...
March 12, 2018: Current Diabetes Reports
Mary Beth Yu, Anthony Firek, William H R Langridge
Rheumatoid arthritis (RA) is an incurable, systemic autoimmune disease that decreases quality of life and can lead to severe disability. While there are many medications available to treat RA, the first-line of therapy is low-dose methotrexate (MTX), a small molecule disease-modifying anti-rheumatic drug (DMARD). MTX is the recommended therapy due to its affordability and efficacy in reducing symptoms in most RA patients. Unfortunately, there is great person-to-person variability in the physiological response to MTX, with up to 50% of patients showing little response to the medication...
March 12, 2018: Inflammopharmacology
Marie Duhamel, Mélanie Rose, Franck Rodet, Adriana-Nathalia Murgoci, Lea Zografidou, Anne Régnier-Vigouroux, Fabien Vanden Abeele, Firas Kobeissy, Serge Nataf, Laurent Pays, Maxence Wisztorski, Dasa Cizkova, Isabelle Fournier, Michel Salzet
High grade gliomas are the most common brain tumors in adult. These tumors are characterized by a high infiltration in microglial cells and macrophages. The immunosuppressive tumor environment is known to orient immune cells towards a pro-tumoral and anti-inflammatory phenotype. Therefore, the current challenge for cancer therapy is to find a way to reorient macrophages toward an anti-tumoral phenotype. Previously, we demonstrated that macrophages secreted anti-tumoral factors when they were invalidated for the proprotein converstase 1/3 (PC1/3) and treated with LPS...
March 12, 2018: Molecular & Cellular Proteomics: MCP
Yoshihito Shima, Yasushi Kawaguchi, Masataka Kuwana
OBJECTIVES: To evaluate the anti-interleukin(IL)-6 receptor antibody tocilizumab (TCZ) as a treatment of systemic sclerosis (SSc), a randomized parallel group study was conducted, and compared their results and baseline cytokine/chemokine profiles. METHODS: Patients were assigned to a TCZ add-on group (TCZ group, n = 7) and a conventional therapy group (Conv group, n = 6). TCZ (8 mg/kg/month) for 6 months, and the modified Rodnan total skin score (mRSS) was used to compare the efficacy...
March 13, 2018: Modern Rheumatology
Andrea Amaroli, Dimitrios Agas, Fulvio Laus, Vincenzo Cuteri, Reem Hanna, Maria Giovanna Sabbieti, Stefano Benedicenti
The literature has supported the concept of mesenchymal stromal cells (MSCs) in bone regeneration as one of the most important applications in oro-maxillofacial reconstructions. However, the fate of the transplanted cells and their effects on the clinical outcome is still uncertain. Photobiomodulation (PBM) plays an important role in the acceleration of tissue regeneration and potential repair. The aim of this in vitro study is to evaluate the effectiveness of PBM with 808 nm diode laser therapy, using a flat-top hand-piece delivery system at a higher-fluence (64 J/cm2 ) irradiation (1 W, continuous-wave) on bone marrow stromal cells (BMSCs)...
2018: Frontiers in Physiology
Michelle L Ratay, Stephen C Balmert, Ethan J Bassin, Steven R Little
Dry eye disease (DED), also known as keratoconjunctivitis sicca, is an ocular surface disease characterized by T-cell-mediated inflammation. Current therapeutics, such as immunosuppressive agents, act to suppress the clinical signs and inflammation. However, long-term usage of these treatments can cause severe side effects. In this study, we present an alternative therapeutic approach that utilizes a histone deacetylase inhibitor (HDACi) to regulate transcription of a variety of immunomodulatory genes. Specifically, HDACi have emerged as a potential anti-inflammatory agent, which can modulate the functions of a subset of suppressive T lymphocytes known as regulatory T cells (Tregs), enhancing FoxP3 acetylation and subsequently guarding the transcription factor from proteasomal degradation...
March 8, 2018: Acta Biomaterialia
E J Ramos González, L J Ramirez Jirano, D Z García Martínez, G G Ortiz, L F Jave Suárez, C A Leal Cortes, O K Bitzer Quintero
INTRODUCTION: Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-β) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-β and GA)...
March 8, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Yvonne Hagenlocher, Sonja Gommeringer, Anna Held, Katharina Feilhauer, Jörg Köninger, Stephan C Bischoff, Axel Lorentz
PURPOSE: Inflammatory bowel disease (IBD) shows increasing prevalence over the last years. We propose that anti-inflammatory plant substances could be used as additional or alternative agents with good compliance in prevention and/or therapy of IBD and its complication intestinal fibrosis. We could recently show that the citrus flavonoid nobiletin acts anti-inflammatory on activation of intestinal mast cells. Here, we analysed the effects of nobiletin on inflammation and fibrosis in IL-10-/- colitis...
March 10, 2018: European Journal of Nutrition
Roxane J Hillier, Elvis Ojaimi, David T Wong, Michael Y K Mak, Alan R Berger, Radha P Kohly, Peter J Kertes, Farzin Forooghian, Shelley R Boyd, Kenneth Eng, Filiberto Altomare, Louis R Giavedoni, Rosane Nisenbaum, Rajeev H Muni
Importance: Variability in response to anti-vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. Objectives: To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. Design, Setting, and Participants: In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017...
March 8, 2018: JAMA Ophthalmology
Minoo Batooei, Ahmad Tahamoli Roudsari, Zahra Basiri, Fatemeh Yasrebifar, Maryam Shahdoust, Azadeh Eshraghi, Maryam Mehrpooya, Sara Ataei
OBJECTIVE: Oxidative stress and Overproduction of pro-inflammatory cytokines are contributed in rheumatoid arthritis (RA) pathogenesis. N-acetylcysteine (NAC) is an antioxidant and anti-inflammatory agent which demonstrated analgesic effects in some studies. This study is designed to assess the effects of oral NAC as an adjuvant therapy on the clinical symptoms of patients with active RA. METHODS: In this randomized clinical trial, 51 RA patients with active RA were studied in 2 groups, NAC group (27 patients) received standard treatment of RA and 600 mg NAC twice a day for 12 weeks and placebo group (24 patients) received the standard treatment of RA and placebo...
March 7, 2018: Reviews on Recent Clinical Trials
A T Hastie, C Steele, C W Dunaway, W C Moore, B M Rector, E Ampleford, H Li, L C Denlinger, N Jarjour, D A Meyers, E R Bleecker
BACKGROUND: The release of various inflammatory mediators into the bronchial lumen is thought to reflect both the type and degree of airway inflammation, eosinophilic Th2, and Th9, or neutrophilic Th1, and Th17, in patients with asthma. AIMS: We investigated whether cytokines and chemokines differed in sputum from subjects with more severe compared with milder asthma, and if unbiased factor analysis of cytokine and chemokine groupings indicates specific inflammatory pathways...
March 9, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Jeffy George, Joseph J Mattapallil
Human immunodeficiency virus (HIV) establishes life-long latency in infected individuals. Although highly active antiretroviral therapy (HAART) has had a significant impact on the course of HIV infection leading to a better long-term outcome, the pool of latent reservoir remains substantial even under HAART. Numerous approaches have been under development with the goal of eradicating the latent HIV reservoir though with limited success. Approaches that combine immune-mediated control of HIV to activate both the innate and the adaptive immune system under suppressive therapy along with "shock and kill" drugs may lead to a better control of the reactivated virus...
2018: Frontiers in Immunology
Naohiro Uezono, Yicheng Zhu, Yusuke Fujimoto, Tetsuro Yasui, Taito Matsuda, Masahide Nakajo, Masahiko Abematsu, Takao Setoguchi, Shuji Mori, Hideo K Takahashi, Setsuro Komiya, Masahiro Nishibori, Kinichi Nakashima
Together with residual host neurons, transplanted neural stem cell (NSC)-derived neurons play a critical role in reconstructing disrupted neural circuits after spinal cord injury (SCI). Since a large number of tracts are disrupted and the majority of host neurons die around the lesion site as the damage spreads, minimizing this spreading and preserving the lesion site are important for attaining further improvements in reconstruction. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern protein that triggers sterile inflammation after tissue injury...
March 8, 2018: Stem Cells
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