Bøger i Progress in Inflammation Research serien

For over 50 years, clinicians have known that macrolide antibiotics have effects on inflammation and the immune system that are not related to their antimicrobial properties. These immunomodulatory properties, best described for treating inflammatory airway diseases, protect the lung and the host and improve clinical status. This book summarizes our current knowledge regarding proposed mechanisms for these properties, established clinical results, and what the future may hold with emphasis on novel clinical applications and the fascinating development of non-antimicrobial macrolides with preserved and enhanced immunomodulatory properties.

Imaging Inflammation provides updates on cutting-edge imaging methods being applied to problems in inflammation research. From state-of-the-art research tools to diagnostic tests, and from single-cell to whole-body imaging, this volume offers a comprehensive overview of how imaging experts across a range of disciplines are expanding our understanding of inflammation and immunity.

This edited collection of 12 chapters by research workers from a wide range of disciplines resolves the confusion that currently surrounds the "e;hygiene hypothesis"e; by considering the human need for exposure to microorganisms from an evolutionary point of view.  The book explains why we evolved a requirement for exposure to microbiota from our mothers, from other people, and from the natural environment. It also explains the physiological roles of these exposures, what goes wrong when the exposures are distorted and how human lifestyles and activities, including degradation of the natural environment, are leading to this distortion.  Particular attention is given to the range of pathologies associated with inappropriate microbial exposures and inappropriate colonization, including immunoregulatory problems such as allergies and autoimmunity, metabolic problems such as obesity and diabetes, and problems of central nervous system function and neurodegeneration.  This book is of profound relevance to most medical disciplines, but also to those concerned with preserving the natural environment and with developing healthier urbanisation.

Over the past ten years, a number of cytokines and growth factors have proven to be as effective therapeutics. While these products have certainly established recombinant biologics as a major pharmaceutical growth sector, the continued interest in this class of drugs arises from the fact that today we have a far better understanding of the human immune response, both at a cellular and molecular level. This has resulted in a more methodical characterisation of these factors which has given clinical researchers an opportunity to plan Phase 1 clinical trials that can provide substantial information on the activity of the cytokine in humans. Currently, a great deal of effort is also being channelled into identifying cytokines from the various DNA databases. Our major objective for this book is to profile cytokines that have been recently identified. The therapeutic potential of these cytokines based on their known properties will be discussed by the authors. The main aim of this book is to provide...

Since the discovery of chemokines and of chemokine receptors it has become evident that expression of chemokines at the site of inflammation may regulate the composition of cellular infiltrate, thereby directing the type of immune response. Recently, the molecular characterization of inherited disorders of immune system, (e.g., Wiskott-Aldrich syndrome, WHIM syndrome, leukocyte adhesion deficiency), which are characterized by cytoskeleton/adhesion defects or by altered response of chemokine receptors has contributed to clarifying the key players of immune response in normal physiology and in disease. This book, which deals with the description of the role of chemokines in immune response and underlines potential targets of therapeutical intervention, offers a series of contributions of the most challenging aspects of lymphocyte migration in homeostasis and in disease.

Chemokines play an important role in recruiting inflammatory cells into tissues in response to infection and inflammation. They also play an important role in coordinating the movement of T-cells, B-cells and dentritic cells, necessary to generate an immune response (response to injury, allergens, antigens, invading microorganisms). They selectively attract leukocytes to inflammatory foci, inducing both cell migration and activation. They are involved in various diseases, like atherosclerosis, lung and skin inflammation, multiple sclerosis, or HIV. Volume 2 of this two-volume set discusses the pathophysiology of chemokines. It is divided into two parts: a) chemokines in animal disease models, and b) chemokines as drug targets. Together with volume 1, which discusses the immunobiology of chemokines, both volumes give a comprehensive overview of chemokine biology.

Scientific interest in regulatory T cells has revived during the last decade. Initially described in the early seventies as suppressor T cells, the concept of suppressor/regulatory T cells went through turbulent times during the eighties when molecular analysis failed to identify putative suppressor genes. The constructive and elegant cellular experiments on regulatory T cells during the nineties, initiated by Shimon Sakaguchi and co-workers, however have brought these cells back into the limelight. Nowadays, regulatory T cells are regarded as essential components of the immune system, and several different subsets of regulatory T cells have been described. Considerable regulatory function has been attributed to the CD4+CD25+ T cell subset. These cells act by suppressing adaptive and possibly also innate immune responses thereby maintaining or restoring the balance between immunity and tolerance. The suppressive effects of CD4+CD25+ regulatory T cells are cell-contact dependent but a role for soluble factors, particularly in vivo, has been suggested as well.The aim of this book is to bring together recent developments and viewpoints in the field of CD4+CD25+ regulatory T cells and to discuss the potential use of regulatory T cells in immunotherapy of inflammatory diseases. By linking data on regulatory T cells from experimental models with recent findings from the clinic, this topical book will be of interest to immunologists and other biomedical researchers as well as clinicians that are interested in regulation and manipulation of the immune response during (chronic) inflammatory disease.

Although the potential for immunomodulation has been recognized for many years there has been an explosion of data in this field with relevance especially to the treatment of chronic airway diseases. Most of the work in this field has been conducted by Japanese investigators but in the last decade there has been a body of work outside of Japan that supports and enhances these findings. The book covers basic research like effects on bacteria, anti-inflammatory and mucoregulatory effects, but also clinical results with up-to-date information for the use of such medications to potentially treat diseases as diverse as chronic airway diseases, arthritis, inflammatory bowel disease, and cancer. The volume is intended for pulmonary physicians, researchers in inflammation research, and pharmaceutical companies interested in the development of such agents. It provides background information for the clinician as well as in depth exploration of cutting edge science.

This book provides comprehensive information, both for clinicians and scientists, on the basic mechanisms, clinical features, and therapeutic approaches to epilepsy as an inflammatory disease. Inflammation has been for many years considered as an etiologic player (and a therapeutic target) for a specific group of epilepsies.

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs).This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade.The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer¿s diseases, and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis andneuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs).This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade.The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer¿s diseases, and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis andneuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

Perinatal psychiatry is an emerging field that investigates the role of perinatal events - for example pregnancy complications and infections - in the development of neuropsychiatric conditions, such as schizophrenia and mood disorders.

Autophagy principally serves an adaptive function to protect organisms against diverse human pathologies, including cancer and neurodegeneration. Recent developments using in vitro, ex vivo and in vivo models show the involvement of the autophagy pathway in immunity and inflammation. Moreover, direct interactions between autophagy proteins and immune signalling molecules have also been demonstrated. Defects in autophagy - similar to cancer, neurodegenerative diseases and aging - through autophagy gene mutation and/or microbial antagonism, may underlie the pathogenesis of many infectious diseases and inflammatory syndromes. In spite of the increasing awareness of the importance of autophagy in these pathophysiological conditions, this process remains underestimated and is often overlooked. As a consequence, its role in the initiation, stability, maintenance, and progression of these diseases are still poorly understood. This book reviews the recent advances regarding the functions of the autophagy pathway and autophagy proteins in immunity and inflammation, focusing on their role in self-nonself distinction, their implications in innate and adaptive immune responses and their dysregulation in the pathology of certain inflammatory and autoimmune diseases.

The role of the cytokine macrophage migration inhibitory factor (MIF) in the immune response and in the immunopathogenesis of different inflammatory, autoimmune, and infectious disorders is now well-established.

This PIR volume presents a comprehensive collection of reviews that focus on the role of the blood-brain barrier (BBB) during steady-state and inflamed conditions. Within the central nervous system (CNS) the constantly changing bloodstream is strictly separated from the CNS parenchyma by the BBB.

Oxidation of polyunsaturated fatty acids by lipoxygenases leads to a variety of fatty acid metabolites which play important roles in physiology but also in pathophysiology.

Further chapters discuss the role of antimicrobial peptides in disease, by providing an overview of mechanisms in bacterial resistance to antimicrobial peptides and a discussion of their role in inflammatory bowel disease, cystic fibrosis lung disease and chronic obstructive pulmonary disease.

The role of the cytokine macrophage migration inhibitory factor (MIF) in the immune response and in the immunopathogenesis of different inflammatory, autoimmune, and infectious disorders is now well-established.

As our understanding of immune mediated chronic inflammatory diseases (IMIDs) grows, it becomes more and more clear that these conditions result from the convergence of a multitude of pathogenic mechanisms whose relative individual contribution is different in different patient subsets.Promising new technologies have been conceived that address the hypotheses that targeting multiple pathways simultaneously, selectively delivering therapeutics to areas of inflammation and/or resetting the immune system, could take efficacy to new levels. However, we have long waited for the arrival of some of these technologies to the bedside, or even far enough in the drug development process in spite of the initial enthusiasm. Some of the examples covered in this book include bispecific antibodies and genomic medicines, microparticles and targeted delivery of drugs to inflamed vasculature.Most published reviews and book chapters on novel therapies for inflammatory diseases describe positive attributes of molecules or technologies under investigation and the rationale for developing them into therapeutics. The originality and potential value of this book is not in the description of these targets or technologies from the point of view of their structure or mechanism of action exclusively, but rather, in making an effort to critically address the question of what is needed to move these technologies into the clinic. Has the technology not made it past the preclinical stage and why? Has it already been tested in humans and failed? What are the potential reasons behind those failures? What do experts in each field believe can be done better to increase the probabilities of success?In addition, the authors address the competitive landscape and summarize clinical studies that have failed in the respective area. They talk about the patient populations that would be required for the successful conduction of a clinical trial to test certain molecules, and they proactively share their views regarding both the potential and the drawbacks of targets or methodologies.

The knowledge of Th17 cells and other cell populations which secrete IL-17A, and/or IL-22 has expanded tremendously since the publication of the first edition "Th17 Cells: Role in Inflammation and Autoimmune Disease" in 2008.

Although T cells represent an important component of the cells which infiltrate the joint synovium, their contribution at a late stage of the disease remains a matter of debate. The goal of this book is to outline the major arguments and data suggesting that T cells may, or may not, be central players in the pathogenesis of chronic RA.

The next area that the book focuses on are effects at the cellular level, on cell survival versus cell death and signals critical for cell function in both normal and disease states.

This volume describes recent research in the field of metalloproteinases (a family of enzymes that can catalyze tissue degradation), in particular their participation in autoimmune diseases such as rheumatoid arthritis, reviewing the latest developments in metalloproteinase inhibitor design and the current status of clinical candidates.