Clinical Applications Of Cytokines And Growth Factors

The driving force for research on cytokines has always been their clinical promise. Their biological properties suggested a key role in hematopoiesis, immunity, tumor genesis, hemostasis, vascularization, repair of connective tissues and integration of the immune system with the neuroendocrine system. Animal studies have shown that cytokines could be used as effective biotherapeutics with easily manageable and reversible toxicities. Clinical trials have confirmed these findings, culminating in the licensing of a number of the cytokines such as interferon alpha, interferon gamma, interleukin 2, erythropoietin, granulocyte colony stimulating factor, and granulocyte-macrophage colony stimulating factor. Many other cytokines are in clinical trials. This is the first comprehensive volume on the cytokines written primarily from a medical perspective. After presenting background information about the structure, production, assays and systemic effects of cytokines and their receptors, it is organized around diseases and organ systems. Infectious diseases, autoimmunity, immunodeficiency states, defective hematopoiesis, allergies, injury repair, cancer, vascular and skin diseases, and neurological disorders are all covered. This work reviews the role that cytokines play in the pathogenesis, diagnosis and therapy of each disease. The authors assess both the current state of the art and the potential for future applications.

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 Second Edition contains a wealth of new information on cytokines and the self-renewal, proliferation, maturation, and state of activity of hematopoietic and immunological progenitor cells and their progeny-demonstrating their efficacy in treating disease states associated with hematopoietic failure or impaired blood cell function. Discusses the demonstrated and potential clinical benefits of hematopoietic growth factors, the economic consequences of using these agents, and various practical usage concerns!

The Second Edition contains a wealth of new information on cytokines and the self-renewal, proliferation, maturation, and state of activity of hematopoietic and immunological progenitor cells and their progeny-demonstrating their efficacy in treating disease states associated with hematopoietic failure or impaired blood cell function. Discusses the demonstrated and potential clinical benefits of hematopoietic growth factors, the economic consequences of using these agents, and various practical usage concerns!

Cytokines are cellular growth factors which also provide communication between cells and their milieu. This clearly is an exciting area in modern medicine that will have significant impact on various facets of transfusion. Erythropoietin therapy stimulates red cell production while thrombopoietin seems to positively affect megakaryopoiesis and can be an added armamentarium for the thrombocytopenic patient. Using haematnopoietic growth factors, stem cells could be mobilized early to the peripheral blood for collection and subsequent transplantation into haemato-oncology patients instead of bone marrow transplantation. Using a cocktail of cytokines in cell culture, stem cells could be expanded and selected for therapy. Cytokines and growth factors can even be modified, which may lead to successful gene therapy in malignancies, including solid tumour vaccines. However, the presence of cytokines in certain blood products could have biological effects following transfusion, although its clinical relevance needs to be ascertained. There is much potential for the use of cytokines in the treatment of infections. Early diagnostic methods are now available to monitor their levels and relevance. It is likely that cytokines will increasingly play a role in therapy and could develop our fundamental knowledge about the development of T-cells. An ethical dilemma remains, however, regarding the use of cytokines in healthy donors for harvesting suitable specific cells. Longer clinical observation will be necessary to gather the necessary information. Cytokines and growth factors in blood transfusion was the theme of the 21st International Symposium in Blood Transfusion, where twenty clinicians and scientists, experts in their own fields, were invited to update the above information. Their findings are presented in four sections in this volume: Fundamental aspects - cytokines in development of T-cells, growth factors in haematopoiesis, growth factor receptors and signal transduction, cytokine response in platelet and whole blood transfusions. Function, production and diagnosis – laboratory diagnostics of cytokines and growth factors, cytokines in blood components, cytokines and growth factors in cell expansions, cytokines for genetic modification towards gene therapy, progenitor cells from healthy donors. Application in clinical medicine – clinical relevance of cytokines in transfusion products, cytokines and growth factors in solid tumours, gene therapy in malignancies, vaccine strategies inducing T-cell immunity against tumours, cytokines in the treatment of infections, thrombopoietin and megakaryopoiesis. Future potential use in transfusion medicine – erythropoietin, immunotherapy, ethical aspects of the use of cytokines and growth factors in donors, potential of cytokines and growth factors in transfusion medicine.

The Second Edition contains a wealth of new information on cytokines and the self-renewal, proliferation, maturation, and state of activity of hematopoietic and immunological progenitor cells and their progeny-demonstrating their efficacy in treating disease states associated with hematopoietic failure or impaired blood cell function. Discusses the demonstrated and potential clinical benefits of hematopoietic growth factors, the economic consequences of using these agents, and various practical usage concerns!

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...