Cytokine Inhibitors

Cytokines have become established as key mediators of the signs and symptoms of inflammatory diseases such as arthritis, dermatitis, asthma and multiple sclerosis. Furthermore, they are involved in the cascade of events leading to cardiovascular shock and are major regulators of the function of immune cells. This book reviews recent advances in the development of new anti-inflammatory drugs. It addresses different therapeutic intervention possibilities for new drugs, such as the cellular source of cytokines, specific receptors which induce cytokine synthesis, intracellular regulators of cytokine gene induction and expression, secretion and activation of cytokines, cytokine receptors and signalling pathways from these receptors. Accordingly, experts were drawn from different backgrounds including academic research institutes, the pharmaceutical industry and clinical pharmacology. In each area, the opportunities for drug development are highlighted and, where possible, clinical data is reviewed.

Compiling an up-to-date and detailed survey of the role cytokines play in cell-to-cell communication, development, and differentiation, this comprehensive reference highlights the medical advantages of cytokine inhibition and pursues novel methods of discovery for more potent and specific blocking agents. Investigates the pathogenic role of cytokines and the potential of cytokine inhibitors as anti-inflammatory, anticancer, antiviral agents! Written by 25 recognized experts revealing recent breakthroughs in research, Cytokine Inhibitors illustrates cases of naturally produced or in vitro engineered polypeptide cytokine blocking agents describes all possible approaches to cytokine inhibitors, including monoclonal antibodies, soluble receptors, engineered mutant cytokines, and small-molecular-weight receptor antagonists and signaling inhibitors clearly explains the homeostatic function of cytokine inhibition and verifies therapeutic approaches effecting natural responses in organisms discusses the results of clinical trials and therapeutic applications of first-generation recombinant receptor antagonists, such as the potential of tumor necrosis factor antagonists as prominent tools in the therapy of chronic inflammatory conditions concentrates on the clinical development of second-generation small-molecular-weight, orally bioavailable cytokine inhibitors reviews the improved understanding of intracellular signaling pathways, the structural determinants responsible for cytokine-receptor interaction lists the three-dimensional structure, relevant receptors, and intracellular tyrosine kinases of cytokines and much more! Containing over 1400 references as well as tables and drawings, Cytokine Inhibitors serves as an exemplary reference for basic and clinical immunologists; allergists; biochemists; pathologists, hematologists; experimental, cell, and molecular biologists; rheumatologists; infectious disease specialists; medicinal chemists; and medical school and upper-level undergraduate and graduate students in these disciplines.

Cytokines are peptide or protein cell-to-cell signaling molecules that play vital roles in normal cell and tissue homeostasis, as well as in responses to infectious agents. Because of their importance in virtually all forms of pathology, the pharmaceutical industry is devoting great effort to develop methods for the control of cytokine synthesis or action. This is the first volume to bring together experts from academia and the pharmaceutical industry to discuss problems and solutions in the therapeutic control of cytokines. An introductory section reviews the biology, physiology, and pathology of cytokines. Internationally recognized scientists then discuss the development of low molecular mass inhibitors, including inhibitors of cytokine convertases and oligonucleotide drugs. The potential use of natural inhibitors such as soluble receptors, interleukin-1 receptor antagonists, and anti-cytokine antibodies is detailed. This interesting book also covers intracellular signaling pathways induced by pro-inflammatory cytokines and the bio-modulatory activity of specific cytokines such as TGF-ß. Therapeutic Modulation of Cytokines will interest academic scientists in biochemistry, cell biology, pharmacology, and molecular biology and biological scientists in the pharmaceutical and biopharmaceutical industries.

Cytokines are the "words" of immunity, serving as mediators within and outside the immune system. There is tremendous interest in their expliotation as therapeutic tools in diverse human diseases and considerable effort has been made to understand and utilize their pharmacology. This book examines this pharmacology, from developments and characterization of simple chemicals and their mechanism of action to the use of biotechnology-based approaches. The book puts cytokines and their pharmacology in context and examines their involvement in individual organ-disease systems.

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...

Within the past few years, it has become recognized that the immune system communicates to the brain. Substances released from activated immune cells (cytokines) stimulate peripheral nerves, thereby signaling the brain and spinal cord that infection/inflammation has occurred. Additionally, peripheral infection/inflammation leads to de novo synthesis and release of cytokines within the brain and spinal cord. Thus, cytokines effect neural activation both peripherally and centrally. Through this communication pathway, cytokines such as interleukin-1, interleukin-6 and tumor necrosis factor markedly alter brain function, physiology and behavior. One important but underrecognized aspect of this communication is the dramatic impact that immune activation has on pain modulation. The purpose of this book is to examine, for the first time, immune-to-brain communication from the viewpoint of its effect on pain processing. It is aimed both at the basic scientist and health care providers, in order to clarify the major role that substances released by immune cells play in pain modulation. This book contains chapters contributed by all of the major laboratories focused on understanding how cytokines modulate pain. These chapters provide a unique vantage point from which to examine this question, as the summarized work ranges from evolutionary approaches across diverse species, to the basics of the immune response, to the effect of cytokines on peripheral and central nervous system sites, to therapeutic potential in humans.