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Cytokine Storm Syndromes, including HLH and MAS, are frequently fatal disorders, particularly if not recognized early and treated during presentation. The genetics of Cytokine Storm Syndromes are being defined with many of the risk alleles giving rise to mutations in the perforin-mediated cytolytic pathway used by CD8 cytotoxic T cells and natural killer cells. These are being studied using murine models. Up to 10% of the general population may carry risk alleles for developing Cytokine Storm Syndromes, and Cytokine Storm Syndromes are being increasingly recognized around the world in pediatric and adult hospitals. A variety of infectious, rheumatic, and oncologic triggers are commonly associated with Cytokine Storm Syndromes, but understanding this disorder is critical for all researchers and physicians to ensure timely and appropriate therapy. This second edition addresses all aspects of the disorder, from genetics, pathophysiology, and ongoing research, to clinical presentations, risk factors and treatment. New-to-this-edition features include dedicated chapters on severe COVID-19 CSS, and post-COVID CSS of multi-system inflammatory syndrome in children (MIS-C). In addition, novel topics including CSS associated with Castleman disease, pregnancy, therapeutics, transplantation, and cardiac bypass, as well as treatment with JAK inhibitors are addressed.

This volume is designed to provide an understanding of current and potential therapies for osteoporosis. The opening chapter introduces the cells of bone and their interactions. Several following chapters describe factors affecting bone including systemic hormones with significant effects on bone, and local mediators including growth factors, prostaglandins, cytokines and chemokines. Topics that have commanded particular attention recently are calcium, FGF-23, nervous system bone interactions. Drugs that cause bone loss provide important information on mechanism as well as therapeutic considerations. An overview of the genetics of bone disorders and a discussion of the pathophysiology of osteoporosis establish the clinical context. The final chapters discuss current and potential osteoporosis treatments.

Cytokine Storm Syndromes, including HLH and MAS, are frequently fatal disorders, particularly if not recognized early and treated during presentation. The genetics of Cytokine Storm Syndromes are being defined with many of the risk alleles giving rise to mutations in the perforin-mediated cytolytic pathway used by CD8 cytotoxic T cells and natural killer cells. These are being studied using murine models. Up to 10% of the general population may carry risk alleles for developing Cytokine Storm Syndromes, and Cytokine Storm Syndromes are being increasingly recognized around the world in pediatric and adult hospitals. A variety of infectious, rheumatic, and oncologic triggers are commonly associated with Cytokine Storm Syndromes, but understanding this disorder is critical for all researchers and physicians to ensure timely and appropriate therapy. This textbook, the first of its kind, addresses all aspects of the disorder – from genetics, pathophysiology, and ongoing research,to clinical presentations, risk factors, and treatment.

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. Recent studies continue to broaden considerably the role of MIF in both normal physiology and pathology, which range from such diverse areas as oncogenesis, metabolism, and cellular stress responses. MIF's molecular mechanism of action in these contexts is becoming increasingly understood and the role of variant MIF alleles in different conditions continues to be defined. New family members, such as D-dopachrome tautomerase, or MIF-2, and the closely homologous genes encoding by parasites have been defined and are being functionally characterized. MIF directed therapies also are entering clinical testing and ultimately may be applied in a pharmacogenomics manner. This book provides a comprehensive synthesis of the state-of-the-art of MIF science. The intended audience are post-graduate students and researchers in inflammation, innate immunity, immunology, and immunopathology.

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. The present volume has been completely revised with the addition of new chapters on the IL-17 receptor family and signaling, and an in-depth review of IL-22 and innate lymphoid cells. The differentiation of naïve T cells into regulatory T cells and Th17 cells as well as the plasticity of Th17 cells is discussed. The role of IL-22 in cutaneous inflammation including psoriasis has been reviewed. In addition, the volume contains critical updates on autoimmunity, organ transplantation, tumor immunology and genetic mouse models for mechanistic studies. Lastly, the latest clinical progress in neutralizing antibodies to IL-17A, IL-17RA not only confirms the therapeutic promise foreseen in 2008, but also improves our knowledge of the pathogenesis of autoimmune diseases. In summary, this is a timely update and important review of the clinical and experimental aspects of IL-17, IL-22 and their producing cells.

The inflammasome was first described in 2002 as a molecular complex activating proinflammatory caspases and therefore regulating the maturation and biological activities of cytokines such as IL-1 and IL-18. This finding was substantiated by the identification of several mutations in the cias1 gene, encoding the human NLRP3 protein, responsible for several autoinflammatory disorders such as the Muckle Wells syndrome. Since, the interest for this complex has constantly increased and several inflammasome complexes with different specificities have been described. These inflammasomes sense a wide variety of pathogens and danger signals and are key players in the inflammatory response. With the contributions of leading international experts in the field, this book provides an extensive overview of the current knowledge of inflammasome biology and their role in health and disease.

Pro-inflammatory cytokines coordinate immune, physiological, metabolic and behavioral responses that are collectively termed the acute phase reaction. In addition to their role in immunoregulation of inflammatory processes, pro-inflammatory cytokines represent the major communication link between peripheral immunity and the central nervous system. Studies in animals have demonstrated that acute activation of pro-inflammatory cytokine signaling in the brain in response to peripheral immune activation is associated with deficits in hippocampal-dependent memory. This book presents and discusses human and animal models studies of the role of cytokines in learning and memory.

The IL-17 cytokines represent a novel family of cytokines, which defines a new effector T cell, the Th17 cell, and extend the Th1-Th2 paradigm. Th17 cells in part co-express at least IL-17A and IL-17F, IL-21 and IL-22. IL-17 A/F are produced by T cells ( and), iNKT cells, and possibly neutrophils, dendritic cells and Paneth cells. The regulation of IL-17 family member's expression, and the identification of effector mechanisms are an area of intense current research. Recognized regulators of IL-17A expression include the nuclear receptor ROR t, proinflammatory cyt- ines such as IL-1, IL-6 with TGF-, IL-21, IL-23 IL-25 in the absence of IFN- and IL-4, which are discussed. Recent data suggest that IL-17A may have a dual fu- tion – pro-inflammatory and anti-inflammatory- suggesting that IL-17A may also contribute to terminate inflammation. Further, a reciprocal regulation of Th17 and regulatory T cells including the role of retinoic acid and TGF- is discussed. The discovery that patients with rheumatoid arthritis, allergic disorders, psor- sis and inflammatory bowel disease express IL-17A generated interest in the medical community and instigated a flurry of experimental research on the potential role of Th17 in inflammatory diseases. Experimental studies confirmed that IL-17A is induced and is critical for the development of allergic lung inflammation, arthritis, bacterial sepsis, experimental allergic encephalomyelitis and myocarditis, as well as other inflammatory con- tions including organ transplantation. The role of IL-17F and IL-22 is still poorly defined and is only slowly emerging.

This book opens a new page of neuro-immunobiology providing substantive experimental and clinical data to support current understanding in the field, and potential applications of this knowledge in the treatment of disease. The volume is a collection of complex, new data drawn from multiple areas of investigation in the field. The contents summarize current understanding on the presence and function of CNS cytokines and their receptors in a variety of CNS cells during health and disease. The chapters are a collection of complex, new data demonstrating the presence and synthesis of cytokines in brain cells, as well as their receptors on cell membranes in health and disease. The strength of the volume are the descriptions of the authors own investigations, together with those of others in the field pertaining to a large number of cytokines in brain function, as well as mechanisms involved in the development of CNS disorders, including multiple sclerosis and Alzheimer's disease. Also included are novel approaches to the treatment of CNS disorders based on new experimental data. The contributors to this volume are internationally known scientists and clinical researchers in their respective fields of investigation and treatment.•Opens a new page of neuro-immunobiology and provides substantive evidence for the promise of this field in the treatment of disease•Summarizes current understanding on the presence and function of central nervous system (CNS) cytokines and their receptors in a variety of CNS cells during health and disease•Includes novel approaches to the treatment of CNS disorders based on new experimental data•Offers new insight into triggers for the development of autoimmune diseases in the brain and the possibilities for treatment

In Septic Shock Methods and Protocols, an interdisciplinary panel of expert investigators describe proven methods for investigating the often deadly mechanisms of septic shock. Drawing on insights from a wide variety of fields-ranging from molecular and cellular biology to the physiological measurement of whole animals-these experienced laboratorians detail the most important techniques for studying sepsis involving endotoxins, toxins derived from gram-positive organisms, cytokines, nitric oxide and other reactive nitrogen intermediates, and the use of primary cell cultures. They also treat a number of significant techniques that are not well described in the literature, including the Limulus endotoxin assay, the bioassay of TNF, the purification of bacterial endotoxin and superantigens, and the culture of primary human cells. Multidisciplinary and state-of-the-art, Septic Shock Methods and Protocols offers both experimental and clinical investigators a gold-standard collection of key methods for illuminating the basic pathophysiological processes that occur following infection. Its readily reproducible methods will allow both newcomers and those with more experience to apply today's powerful techniques successfully in their work.

Cytokine Cellular Biology focuses on cell biology techniques for studying cytokines, cytokine receptors, and cytokine driven processes. Assays for human B cell responses, leucocyte migration, haematopoietic growth factors, macrophage activation by cytokines, RIA, IRMA, and ELISA assays, and quantitative biological assays for cytokines are all covered in detail. There are also updated chapters on studying cytokine regulation of endothelial cells; the measurement of proliferative, cytostatic, and cytolytic activity of cytokines; and the development of antibodies to cytokines. In addition there is a new chapter on the use of flow ctyometry and intracellular fluorescent staining. Written by experts in the field, Cytokine Molecular Biology and Cytokine Cellular Biology form a comprehensive and essential guide to cytokine research.

International Review of Experimental Pathology, Volume 34: Cytokine-Induced Pathology Part B: Inflammatory Cytokines, Receptors, and Disease presents experimental findings obtained from the most recently studied cytokines and growth factors. The book is organized into three sections. Section I contains studies on pathology induced by inflammatory cytokines. Topics covered include the biological effects of interferon-?, tumor necrosis factor- a (TNF), interleukin-8, transforming growth factor-ß, and leukemia inhibitory factor on experimental animals; TNF-induced pathophysiologic alterations; and the biological activity of leukemia inhibitory factor (LIF). The papers in Section II examine cytokine receptors, including their structure and signal transduction; interferon-? (IFN-?) activity; and immunoregulatory role of TNF-a. Section III is devoted to cytokine receptors, including studies on TNF properties relevant to tissue injury and its role in T cell-mediated immunopathological reactions in vivo; the role of cytokines in experimental pulmonary fibrosis induced in mice; and the role of cytokines in bacterial meningitis.

Neurobiology of Cytokines, Part A provides an overview of the effects of cytokines in the brain and in the endocrine system. The book discusses the general aspects of cytokines, including the endogenous agonists and antagonists, their receptors, their second messengers, and transport mechanisms for cytokines across the blood-brain barrier. The text also describes the anatomical localization of cytokines, cytokine receptors, and their respective mRNA in brain and in endocrine tissues. The methods for evaluating the in vivo as well as in vitro actions of cytokines on hormone secretion are also considered. The book further tackles the synthesis and release of cytokines and their central nervous system actions; and the methodology for studying the role of cytokines in human neuropathological conditions.

Recent data suggest a critical role for cytokines in the regulation of brain and endocrine function under normal physiological conditions. The aim of this volume and its companion Volume 16 is to provide an overview of the effects of cytokines in the brain and in the endocrine system. Methods presented for easy adaptation to new systems Comprehensive protocols included for: The synthesis and release of cytokines; The study of their central nervous system actions; Studying the role of cytokines in human neuropathological conditions