Carrying on the high standards of the much praised first edition (Durum and Muegge, Cytokine Knockouts, 1998), Giamila Fantuzzi and a panel of experts have generated completely new chapters to reflect the use of many novel mouse strains and the hundreds of recent studies on cytokine physiology. Comprehensive reviews of the numerous often-surprising results obtained using cytokine knockout mice are provided, along with much important information about cytokine biology and physiology. For those not familiar with cytokine research, the authors present a critical discussion of the advantages and disadvantages of using cytokine knockout mice in various fields of research.

My personal history in the field of cytokines had an initial period of several years during which my student and then colleague, Werner Muller, tried in vain to attract me to them. My interest always vanished when I was confronted with complex data pointing to func tional redundancy of cytokines in cell culture systems. When gene targeting in the mouse germline became possible, this frustration came to an end. We and others immediately embarked on analyzing the in vivo function of cytokines and the problem of functional redundancy with this powerful new approach. The early cytokine gene knockouts performed by colleagues in Wiirzburg (IL-2) and by ourselves (IL-4 and IL-l 0) seemed to give clear answers and at the same time led to surprises: Each of these cytokines apparently had its own special and irreplaceable function, and this function could be quite distinct from what had been anticipated from functional experiments in vitro. Al though the latter finding is of course a wonderful incentive for fur ther research, the former is pleasing in a general sense since it highlights the value of each of those one hundred thousand genes or so in our genome, cherished by evolution to become respectable mem bers of the community. Even in the present era of "genomics" there will be no way around the careful functional analysis of each gene by itself.

Every aspect of immune function and host defense is dependent upon a proper supply and balance of nutrients. Severe malnutrition can cause significant alteration in immune response, but even subclinical deficits may be associated with an impaired immune response, and an increased risk of infection. Infectious diseases have accounted for more off-duty days during major wars than combat wounds or nonbattle injuries. Combined stressors may reduce the normal ability of soldiers to resist pathogens, increase their susceptibility to biological warfare agents, and reduce the effectiveness of vaccines intended to protect them. There is also a concern with the inappropriate use of dietary supplements. This book, one of a series, examines the impact of various types of stressors and the role of specific dietary nutrients in maintaining immune function of military personnel in the field. It reviews the impact of compromised nutrition status on immune function; the interaction of health, exercise, and stress (both physical and psychological) in immune function; and the role of nutritional supplements and newer biotechnology methods reported to enhance immune function. The first part of the book contains the committee's workshop summary and evaluation of ongoing research by Army scientists on immune status in special forces troops, responses to the Army's questions, conclusions, and recommendations. The rest of the book contains papers contributed by workshop speakers, grouped under such broad topics as an introduction to what is known about immune function, the assessment of immune function, the effect of nutrition, and the relation between the many and varied stresses encountered by military personnel and their effect on health.

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.

The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

The hematopoietic system plays roles that are crucial for survival of the host: delivery of oxygen to tissues, arrest of accidental blood leaking from blood vessels, and fending off of invading microbes by humoral, cell-mediated, and phagocytic immunity. The activity of the hematopoietic system is staggering: daily, a normal adult produces approximately 2.5 billion erythrocytes, 2.5 billion platelets, and 1 billion granulocytes per kilogram of body weight. This production is adjusted in a timely fashion to changes in actual needs and can vary from nearly none to many times the normal rate depending on needs which vary from day to day, or even minute to minute. In response to a variety of stimuli, the cellular components of the blood are promptly increased or decreased in production to maintain appropriate numbers to optimally protect the host from hypoxia, infection, and hemorrhage. How does this all happen and happen without over or under responding? There has been extraordinary growth in our understanding ofhematopoiesis over the last two decades. Occupying center stage is the pluripotent stern cell and its progeny. Hematopoietic stern cells have been characterized by their capacity for self renewal and their ability to proliferate and differentiate along multiple lineages. Few in number, the stern cell gives rise to all circulating neutrophils, erythrocytes, lymphoid cells, and platelets. In hematopoietic transplantation, the stern cell is capable of restoring long-term hematopoiesis in a lethally irradiated host.

The number of cytokines and related growth factors has increased dramatically in recent years to several dozen. This text provides a succinct reference manual for all known cytokines, growth factors, interleukins and lymphokines as well as their receptors.

This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.

Advances in itch research have elucidated differences between itch and pain but have also blurred the distinction between them. There is a long debate about how somatic sensations including touch, pain, itch, and temperature sensitivity are encoded by the nervous system. Research suggests that each sensory modality is processed along a fixed, direct-line communication system from the skin to the brain. Itch: Mechanisms and Treatment presents a timely update on all aspects of itch research and the clinical treatment of itch that accompanies many dermatological conditions including psoriasis, neuropathic itch, cutaneous t-cells lymphomas, and systemic diseases such as kidney and liver disease and cancer. Composed of contributions from distinguished researchers around the world, the book explores topics such as: Neuropathic itch Peripheral neuronal mechanism of itch The role of PAR-2 in neuroimmune communication and itch Mrgprs as itch receptors The role of interleukin-31 and oncostatin M in itch and neuroimmune communication Spinal coding of itch and pain Spinal microcircuits and the regulation of itch Examining new findings on cellular and molecular mechanisms, the book is a compendium of the most current research on itch, its prevalence in society, and the problems associated with treatment.