Cytokines In The Brain

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

It is now accepted that immune molecules are not only present within the brain during pathology but they exert physiological functions in the “healthy” brain as well. Increasing evidence points to a neuro-modulatory role of cytokines and chemokines (CHEMOtactic cytoKINES) in basal transmission and plasticity processes where signaling between peri-synaptic astrocytes, microglia and neurons plays an important role. Nevertheless, the exact mechanisms as to how cytokines, and in particular chemokines, participate in the molecular and cellular processes thought to subserve memory formation, plasticity processes and responsiveness to environmental stimuli remain to be clarified. Interestingly, in in vitro preparations, molecules like TNF-α, interleukin (IL)-1β, IL-6, CX3CL1, CXCL12, CCL2 and CCL3 are implicated in synaptic formation and scaling, in modulation of glutamatergic transmission, in plasticity and neurogenesis, in particular in the hippocampus. The hippocampus is an extremely plastic structure, one of the main neurogenic niches in the adult brain, that exhibits a marked sensibility to environmental stimuli. Indeed exposure of mice to environmental enrichment (EE) modifies learning and memory abilities increasing neurogenesis and neuronal plasticity whether exposure to severe stressful experiences diminishes neurotrophic support, impairs neurogenesis, plasticity and cognition. In the hippocampus cytokines play a key role in mediating both positive as well as negative effects of the environment affecting neuronal plasticity also in stress related pathologies, such as depression. It has been reported that mice lacking type 1 receptor for IL-1 display impaired hippocampal memory and LTP that are restored by EE; moreover negative effects on neuronal plasticity (and thus behavior) induced by stress exposure can be prevented by blocking IL-1 activity. In addition, mice lacking IL-6 have improved cognitive functions whereas the absence of microglia-driven CX3CR1 signaling increases hippocampal plasticity and spatial memory occluding the potentiating effects of EE. However, the factors mediating the effect of environmental stimuli on behavior and plasticity has been only partially identified. Interestingly, it has been suggested that chemokines can play a key role in the flexibility of hippocampal structure and may modulate neuronal signaling during behavior. The question is how cytokines may translate environmental stimuli in plasticity and behavioral changes. This research topic is proposed to explore the role of cytokines, and more in particular chemokines, in the modulation of neuronal activity as a fundamental step for the correct brain wiring, function and susceptibility to environment. We encourage the submission of original research reports, review articles, commentaries, perspectives or short communications, in the following (but not limited to) topics: - Role of cytokines and chemokines in neuronal plasticity - Immune molecules and responsiveness to environment - Role of chemokine in the flexibility of hippocampal structure

Interest in interleukin-1 (IL-1) has increased dramatically over the last decade, but has been largely restricted to immunologists, cell biologists and those studying inflammation and cancer. However, it has recently been recognized that the brain directly controls or modulates many aspects of immune function, while molecules classically associated with the immune system, such as interleukin-1, are synthesised within the brain and act directly on the central nervous system to modify local and systemic functions. Thus, this topic is relatively new to neurobiologists, and this book is the first comprehensive description of current knowledge on interleukin-1 in the brain, including its location, synthesis and receptors, actions on behaviour, fever, metabolism, neuroendocrine function, electrical activity of the brain, nerve growth factor, and relationship to clinical indications. The book is organised into three sections. The first reviews the data available on the neural localisation of IL-1 and the nature of its central receptors. The main part of the book examines the different neural effects of IL-1 and the mechanisms which are involved in these actions, comparing IL-1 where possible to other inflammatory cytokines which also have neurotrophic effects. The final section evaluates the possible role of IL-1 in neural plasticity and neuronal degeneration.

Provides Insight into How Cytokine Action Impacts the Physiology and Pathology of the CNS. As with the first edition of Cytokines and the CNS, this completely updated and revised edition introduces neurobiologists to cytokine biology and immunologists to the unique functions of cytokines in CNS physiology. The dramatically accelerating interest in cytokines and cytokine/chemokine signaling over the past several years has encouraged an explosion of literature on cytokines. The similarity between factors involved in inflammation or immunity, and those implicated in neural development, physiology, and repair has become so apparent that familiarity with cytokines must now be considered an essential element in the neurobiologist’s cognitive tool-kit. Conversely, for immunobiologists, the concepts elaborated by neurobiologists to understand developmental patterning and networked organ function continue to evolve in such a way that comprehension of cytokine action in the CNS can only enhance a further understanding of immune system function. Cytokines and the CNS, Second Edition is patterned after the first edition; however, the wealth of knowledge now available adds a tremendous amount of insight and new implications. To guarantee a fresh perspective, the editors made a conscious choice to utilize an entirely new set of contributors, all experts in various aspects of cytokine research. Cytokines and the CNS, Second Edition starts with a chapter on the CNS, focusing on pathological reactions to insult. Next, come three chapters on cytokine biology, followed by four chapters that integrate cytokine biology into basic CNS processes (development; inflammation; immunity; degeneration/repair), after which five chapters apply this body of knowledge to disease or pathology. The book closes with a look at the application of cytokine biology to the treatment of disease, a brand new area of research.

From the reviews: ""Brain Neurosecretory Cytokines is an excellent book, a veritable goldmine of information, at the cutting edge of neuroscience. It should stimulate ideas for future directions in neuroscience for years to come. This volume should be highly useful for medical libraries, neuroscientists, endocrinologists and graduate students in these fields."" (Arthur S. Brecher, TRENDS in Endocrinology & Metabolism, Vol. 16 (6), 2005)

For many years, the immune and central nervous systems were thought to function independently with little or no interaction between the two. This view has und- gone dramatic changes over the past three decades. Indeed, we now know that there exists various feedback loops between the brain and immune systems that impact signi cantly upon different behavioral processes, including normal behavior and mental disorders. Pioneering efforts in generating this change were initiated by a number of early investigators. Included were those whose efforts were directed at establishing neuroimmune connections as well as others whose research focused upon the relationship between immunity, cytokines, and behavior. This book brings together outstanding scientists and clinicians who have made major contributions to the rapidly developing eld investigating the relationship between immunity and behavior. The book is divided into three parts. The rst part describes pathways by which the brain and immune systems communicate and int- act with each other. In the chapter “Cytokines and the Blood–Brain Barrier” p- vides insight into interactions between the blood–brain barrier and cytokines. Such interactions underlie basic communication between the immune system and brain that are present in normal as well as in disease conditions. In the chapter “Neu- chemical and Endocrine Responses to Immune Activation: The Role of Cytokines,” the neurochemical and endocrine consequences of immune challenge and cytokine administration on central neurotransmitter activity are discussed.