Articles That Use the Tag Name:

proinflammatory cytokine

Treating IgA Nephropathy: Quid Novi?

Abstract: IgA nephropathy is a common autoimmune renal disease resulting in kidney failure for patients with significant proteinuria. The therapeutic options are limited including non-specific treatment to reduce proteinuria accomplished by renin-angiotensin blockade. Strategies to control intrarenal inflammation include the administration of fish oil and for severe disease the use of immunosuppressive agents such as cyclophosphamide, glucocorticosteroids, and mycophenolate mofetil. In light of the limited option, there is an unmet need for novel therapeutic intervention in patients with progressive disease. Herein, we review the evidence for existing treatment choices and explore new immunopharmacologic agents being investigated for IgA nephropathy. ... Read more

Novel Insight into the Role of Alpha-actinin-1 in Rheumatoid Arthritis

Abstract: The knowledge of rheumatoid arthritis (RA) pathology is rapidly advancing and becoming more and more complex, and a simple fact is that the major organ targeted by RA pathogenic factors is the synovium. It is well known that fibroblast-like synovial (FLS) cell is the major cell-type for constructing synovium. Following stimulation by pro-inflammatory cytokines, FLS cells are phenotypically changed to have the capability to proliferate abnormally. Recently we demonstrated that α-actinin-1 (ACTN1) gene is significantly increased in synovial tissues obtained from RA, as compared to osteoarthritis (OA). We therefore reviewed the literature about α-actinins (ACTNs) and we now propose that ACTN1 may function as a "terminal effector" of intracellular signalings initiated by tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in RA. Future research on ACTN1 may help to improve the current therapeutic and diagnostic strategies of RA. ... Read more

Combination of Virotherapy and T-cell Therapy: Arming Oncolytic Virus with T-cell Engagers

Abstract: While cure rates for several cancers have significantly improved, the outcome for patients with advanced solid tumors remains grimly unchanged over the last decades. Thus, there is a need for new therapies that could improve outcome for patients who fail current therapies. Oncolytic (cancer destroying) vaccinia virus (VV) would be an appealing addition to the current therapies of cancers because of its ability to infect, replicate in, and lyse tumor cells, and spread to other tumor cells in successive rounds of replication. While clinical studies have demonstrated their safety, the antitumor efficacy of oncolytic VVs has been suboptimal. Oncolytic VVs' major mode of action is the destruction of tumor cells, which can subsequently activate a component of the immune system called T-cells that can travel to distant sites and target against any tumor they find. At present, virus spread through tumors, as well as the activation of tumor-specific T-cells, is limited, explaining the observed suboptimal antitumor activity of current oncolytic VVs. Thus it would be desirable to make the oncolytic VVs more powerful stimulators of immunity through activating resident T-cells within the tumors so that they will kill tumor cells and stop new tumors from growing. To activate T-cells within tumors, a new molecule called a T-cell engager that couples the T cell and the tumor cell, which increases the effectiveness of the T cells and their activation, has been constructed. This review summarizes the progress of the emerging field of combinations of oncolytic virotherapy and T-cell based therapy. ... Read more

Scleritis: Challenges in Immunopathogenesis and Treatment

Abstract: Scleritis is an uncommon disease characterized by inflammation of the sclera and adjacent ocular structures. Recent studies have led to significant progress in understanding the epidemiology, immunopathogenesis, severity assessment, treatment, and prognosis of this potentially sight threatening disease. Despite these advances, significant challenges remain regarding our understanding of the mechanisms of scleral destruction and inflammation, and the rational approach to treatment. Information from studies in associated systemic diseases and vasculitis and a small number of studies of ocular tissue has revealed the prominent role of T and B cells, autoantibodies, immune complexes, and cytokines, such as TNF-alpha. These studies have prompted clinical trials that have demonstrated the effectiveness of anti-TNF, anti-B cell therapy, systemic immunosuppression, and more recently the use of local sub-conjunctival steroid treatment. ... Read more

Adipokines: Novel Players in Rheumatic Diseases

Abstract: A large body of evidence from clinical and experimental studies is aiding to understand the close relationships between obesity and rheumatic diseases. For instance, it is generally accepted that obesity contributes to the development of osteoarthritis by increasing mechanical load of the joints, at least in weight bearing joints. However, besides mechanical effects, recent studies demonstrated that white adipose tissue is able to secrete a plethora of soluble factors, called adipokines, which have a critical role in the development and progression of some rheumatic diseases such as osteoarthritis and rheumatoid arthritis. In this article, we summarize the recent findings on the interaction of certain adipokines with the two most common rheumatic diseases: osteoarthritis and rheumatoid arthritis. ... Read more

Relevance of the Type I Interferon Signature in Multiple Sclerosis Towards a Personalized Medicine Approach for Interferon-beta Therapy

Abstract: Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system. The disease is characterized by progressive neurological dysfunction due to demyelination of the nerves, which leads to disability. Currently, no curative therapy is available and patients are subjected to a prolonged course of treatment. Interferon-β (IFNβ) was the first agent to show clinical efficacy in the treatment of MS, and is still the best available therapy. Unfortunately, clinical experience indicates that approximately 40% of the patients do not or only poorly respond to IFNβ treatment. Recent advances revealed the presence of an activated type I IFN pathway in a subset of treatment naïve patients with relapsing remitting MS (RRMS), as shown by the presence of an "IFN signature" and type I IFN bioactivity in the blood of these patients. Evidence exists that quantification of the IFN signature in RRMS is informative as a biomarker to predict the clinical response to IFNβ. In this review we summarize the current evidence of type I IFN activation in RRMS and its clinical relevance. ... Read more

Elusive Alzheimer's Disease: Can Immune Signatures Help Our Understanding of This Challenging Disease? Part 2: New Immune Paradigm

Abstract: Alzheimer's disease (AD) is the most common form of dementia. Its most important pathological hallmarks are profound neuronal loss, presence of intracellular neurofibrillary tangles, and extracellular deposition of beta-amyloid protein (Aβ) as beta-amyloid plaques. One of the most important risk factors for AD is age and with the increase of life-expectancy AD has become the most common form of dementia. The current "Holy Grail" is to be able to diagnose variants of AD before they manifest clinically and before irreparable brain damage is done. To be able to do so, we need robust and reliable biomarkers which reflect the pathogenesis of AD. This is essential because such biomarkers might indicate pathways that could be targeted for interventions aiming at disease prevention or amelioration. Although much attention has been focused on Aβ in this respect, it may not be as attractive a target as thought if current doubts concerning its causative role are substantiated. This review will be in two parts, the first part dealt with the current clinical knowledge and the questions raised by the Aβ cascade hypothesis in the pathogenesis of AD and this second part aims to synthesize our current knowledge and new data suggesting how immunity may contribute to the development of AD and may itself be targeted in future treatments. ... Read more

Emerging Trends in Biological Therapy for Intervertebral Disc Degeneration

Abstract: Intervertebral disc disease is characterized by a series of deleterious changes in cellularity that lead to loss of extracellular matrix structure, altered biomechanical loading, and symptomatic pain. At present the "gold standard" of therapy is discectomy -- surgical removal of the diseased disc followed by fusion of the adjacent vertebral bodies. The procedure alleviates pain, but fusion limits range of motion and alters the mechanical loading at other spinal levels, hastening disease at previously unaffected sites. Biological therapeutics have the potential to repair damaged tissue by several means: (1) altering cell phenotype to regenerate matrix components, (2) augmenting tissue with reparative cells, (3) delivering bioactive materials to reestablish disc biomechanics and serve as a template for cell-based regeneration. Although research into biological treatments for disc degeneration has been ongoing for over a decade, few treatments have progressed to clinical testing and none are currently commercially available, primarily due to a limited understanding of disease etiology. Further work is needed to identify targets and interventional time points as disc degeneration progresses from early to later stages. This review focuses on emerging trends in biological treatments and identifies key obstacles to their clinical translation. ... Read more

Rheumatoid Arthritis and Alzheimer's Disease: Genetic and Epigenetic Links in Inflammatory Regulation

Abstract: Controversial data are available about the relationship between Alzheimer's disease (AD) and rheumatoid arthritis (RA). An inverse relationship between AD and RA, due to different factors, was previously described. Similarly to RA, AD pathogenesis is multifactorial and different findings support the inflammatory pathogenetic hypothesis. Several inflammatory mediators are involved in the disease onset and progression regulated by genetic and epigenetic mechanisms. Among them, inteleukin-6 (IL-6) and interleukin-1 (IL-1) as pro-inflammatory soluble factors produced by monocytes-macrophages and tumor necrosis factor alpha (TNF-α) produced by activated macrophages and mononuclear cells represent key molecules in the induction and maintenance of chronic inflammation in RA. In particular a link with the T allele of the SNP 3953 T/C in the IL-1 gene and an overexpression of miR-146a appears to be common to both RA and AD. In this review we will discuss the genetic and epigenetic regulation of the inflammatory cascade in RA and AD to find out the possible links between RA and AD onset. ... Read more

Sympathetic Overactivity and Cardiovascular Disease in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Abstract: Cardiovascular disease plays an important role regarding the morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Sympathetic overactivity has been suggested to underpin the association between COPD and the development of cardiovascular disease. However, the pathophysiological basis by which sustained sympathetic overactivity affects cardiovascular function in patients with COPD is complex and incompletely understood. Different simple and more sophisticated measures of sympathetic activity, such as assessment of heart rate, blood pressure variability, and baroreflex sensitivity, provide information on the potential dysregulation of the autonomous nervous system. This review summarizes the findings from studies in animal models and humans on the potential relationship between COPD, sympathetic overactivity, and cardiovascular disease. There is preliminary evidence of sympathetic overactivity in COPD. However, direct evidence of a cause-effect relationship between sympathetic overactivity and cardiovascular disease from studies in COPD patients is lacking. Data from large cohorts of COPD patients and well-designed interventional studies looking at the relationship between COPD and autonomic nervous system function are urgently needed, hopefully leading to novel therapeutic and preventive approaches in the care of patients with COPD. ... Read more

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