The Cytokine Network and Immune Functions
The Cytokine Network and Immune Functions
J. Thèze, editor
New York (NY): Oxford University Press; 1999. 373 pp with index
ISBN 0-19-850136-6 (cloth)
Like the brain, which orchestrates behaviour principally through the secretion by neurons of various neurotransmitters that act on other neurons, the immune system displays similar finesse by synthesizing and secreting a large variety of chemical messengers, generically referred to as “cytokines.” As readers of The Cytokine Network and Immune Functions will appreciate, this function of the immune system is no less complex and exquisitely sophisticated than the exchange of information between neurons in the brain or the response of endocrine tissues to hormones. Indeed, from a behavioural perspective, the immune system — like the brain — evolved to mediate defensive functions that would optimize successful adaptation and survival. Whereas the brain scans and processes information in response to stimuli with circumscribed physical and sensory dimensions, the immune system performs similar functions at a molecular level, responding to viruses and bacteria that our more traditional senses are unable to perceive. Ultimately, the “foreigness” of viruses and bacteria elicits a coordinated set of defensive actions (what immunologists call an effector function) by a variety of immunological cells that ultimately rids our bodies of the would-be colonizers.
What this book summarizes in some detail, is that from the point of initial pathogenic stimulus exposure to the ultimate effector response, the defensive functions of the immune system are orchestrated by several families of cytokines, acting in coordinated fashion — as a network — and mobilizing in cascade fashion, and according to specific needs, the fatal blow to foreign microorganisms.
However, all networks possess the potential for dysregulation. Hence, aberrant cytokine responses are believed to be responsible for allergies, asthma and numerous autoimmune disorders. Moreover, there is a growing recognition that cytokines can affect brain function. Unfortunately, this is exclusively addressed in only a single — and lamentably, brief — chapter (”Cytokines in the brain” by Laye et al). Additional indirect treatment of the relation between neuroendocrine function (e.g., the hypothalamic-pituitary-adrenal axis) and cytokines is rendered in a chapter on cytokines and inflammation (”Cytokines and the cellular mechanisms of inflammation” by Cavaillon and Duff). Therefore, for researchers and practitioners in the brain sciences, there is little in this volume that cannot be obtained in other publications that provide a more comprehensive discussion of the relation between the immune system, cytokines and neural and behavioural functions.
Alternatively, a considerable amount can still be learned about basic cytokine biology, receptors and signal transduction mechanisms. To echo the foreword by William Paul, which was perhaps directed to a more immunological audience, there is much in this book that can greatly inform and equip those of us involved in research in neuroimmunology and the behavioural consequences of immune responses and inflammation. Indeed, subsets of mood disorders, such as dysthymia, have been hypothesized to involve an autoimmune component that is mediated by cytokine dysregulation. Similarly, multiple sclerosis is an autoimmune disorder, but with severe depressive symptomatology and cognitive deficits. A greater knowledge of cytokines and their cellular actions at the molecular level would certainly enhance efforts toward understanding central nervous system diseases that involve the immune system. In fact, this book is probably indispensable to all whose work involves cytokines, no matter what biological system is being scrutinized.
As witnessed in recent years, the leaps-and-bounds advance in molecular biology has not so much rippled, as ripped its way through much of the biological sciences, and as readers of The Cytokine Network and Immune Functions will no doubt appreciate, has also served to propel the study of cytokines. For example, it was not that long ago that the number of known cytokines could be counted on a single hand. However, currently, and as well described in the book, cytokines are bunched into at least 6 families, based on the structure and characteristics of the receptors to which they bind (i.e., the hematopoietin, interferon, tumour necrosis factor, interleukin-1 and chemokine receptor families and the immunoglobulin superfamily). For the uninitiated, this may be somewhat perplexing and confusing, but an introductory overview chapter (”General aspects of cytokine properties and functions” by Dy et al), although not exactly smooth sailing because of a plethora of abbreviations and acronyms that do not fall immediately into coherent place, does prepare the reader for the tone and level of complexity in subsequent chapters. For those comfortable with molecular levels of analysis, these should not be turbulent waters. However, those wishing a more superficial description of cytokines and their functions may find the going tough. This book is not light reading, but it is a well-organized and broad overview for those who are serious about wanting to know more about cytokine biology. Indeed, seasoned researchers and teachers of immunology will easily find it a valuable resource in a field that is incredibly dense with information and complexity.
The organization of chapters revolves around 3 sections, beginning with basic, fundamental discussions and moving on to more immunobiological and clinical considerations. In the first and largely molecular section, chapters are devoted to classes of cytokines, such as the hematopoietin or class I receptor family of cytokines (e.g., interleukins 2,4, 7,9,13 and 15), as well as specific chapters on individual cytokines, including tumour necrosis factor, interleukin-1, interleukin-6, interleukin-10, inter-leukin-12 and transforming growth factor (3. There is also a chapter devoted to the Type I (wherein there are up to 21 different types) and Type II (viz., interferon y) interferons, as well as an update on more recently discovered cytokines (interleukins 16, 17 and 18). These chapters characterize the biochemical structure, genetics and cellular origins of these cytokines as well as describe the localization and structure of their receptors. Additional chapters also address signal transduction mechanisms, the role of accessory surface molecules (e.g., CD40) in cytokine regulation of function and cytokine gene regulation.
These initial 13 chapters are followed by 7 chapters that consider cytokines within their biological context, largely the immune system, but as mentioned above, also in the brain. The immunological profile of mice with deletions and/or overexpression of various cytokine genes and/or their receptors is discussed, as is the role of cytokines in immunological development. In addition, separate chapters address the way in which cytokines regulate specific (e.g., T cells) and nonspecific (e.g., macrophages) arms of the immune system. This segregation ultimately reveals a great deal of overlap, because it has become clear that many cytokines are pleiotropic and redundant.
The book concludes with a section on pathological conditions, wherein cytokine dysregulation is believed to either be at the root of various diseases (i.e., allergies, asthma, infectious disease, autoimmune disorders and cancer) or, conversely, where their immunotherapeutic use may promote recovery from disease.
The book accomplishes its goal of attempting to provide a more synthetic and “network-oriented” view of how cytokines serve their purpose. The treatment is broad, and of course, at some expense. There appears to have been a conscious effort to emphasize facts and predominant points of view, giving the book a textbook quality. In-text citations are not provided, although each chapter does conclude with a reference list. Therefore, one should look to this book, not as a literature review, but more an informed statement of the current state of knowledge in cytokine immunobiology.