Clinical Applications of Cytokines: Role in Pathogenesis, Diagnosis, and TherapyJoost J. Oppenheim, Jeffrey L. Rossio, A. J. H. Gearing 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. |
Contents
Section IIntroduction to Cytokine Biology | 3 |
Measurement of Cytokines | 16 |
Regulation of the Acute Phase Response by Cytokines | 27 |
Section IIInfectious Diseases and Immunodeficiency States | 35 |
Role of Cytokines in Bacterial Infections | 43 |
Cytokines and Parasitic Diseases | 49 |
Role of Cytokines in Pulmonary Diseases | 61 |
Role of Cytokines in Chronic Granulomatous Inflammation | 67 |
Monoclonal Antibodies Against Receptors for Cytokines as Potential | 195 |
Section VHematopoietic Disorders | 201 |
Cytokines for Treatment of Bone Marrow Failure Syndromes | 207 |
Role of Cytokines in Bone Marrow Transplantation | 217 |
Therapeutic Utility of Cytokines in Counteracting Bone Marrow Suppression | 225 |
Erythropoietin | 237 |
Section VIAllergic and Cutaneous Disorders | 245 |
Recruitment of Inflammatory | 251 |
yInterferon | 75 |
Cytokines and Human Retroviruses | 93 |
Section IIIAutoimmune Disorders | 94 |
Cytokine Therapy for IL2 Deficiency | 105 |
Role of Cytokines in Autoimmune Disease | 109 |
Cytokines and Rheumatoid Arthritis | 115 |
Cytokines and Type I Diabetes | 123 |
Section IVNeoplastic Diseases | 129 |
Interferon Therapy for Malignant and Nonmalignant Disease | 135 |
Interleukin2 Therapy for Human Cancer | 147 |
Evaluation of Interleukin1 as an Anticancer Agent | 155 |
Pathophysiologic Effects of Tumor Necrosis Factor Therapy on Cancer Patients | 165 |
A Potential Antitumor and Antiinflammatory Agent | 171 |
Role of Cytokines in BCell Tumors | 177 |
Effects of Local Cytokine Therapy | 187 |
Section VIICytokine Antagonists | 257 |
Recombinant Toxins Directed to Cytokine and Growth Factor Receptors | 263 |
Immunosuppressive Drugs Acting Through Blockade of Cytokine Expression | 269 |
Section VIIIVascular Disorders | 275 |
Modulators of Endothelial Cell Activity in Neovascularization | 283 |
Cytokines and Coagulation | 293 |
Section IXTrauma and Repair | 301 |
Role of Cytokines in Wound Repair | 307 |
Cytokines in Muscle Homeostasis and Disease | 329 |
Mechanisms | 337 |
Cytokines and Bone Remodeling | 347 |
Section XNeurological Problems | 357 |
Role of Cytokines in Peripheral Nervous Tissues | 367 |
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Acad activity acute phase administration anemia angiogenesis antigen antitumor arthritis assay binding Biol cachexia carcinoma cell lines cellular chemotherapy chronic Clin clinical trials clones colony-stimulating factor cultures cytokines cytotoxic detected DINARELLO disease dose effects endothelial cells enhanced epidermal growth factor erythropoietin expression function gene GM-CSF granulocyte granuloma hematopoietic hepatitis HTLV-I IFNa IFNy IL-2 receptor Immunol increased induced infection inflammatory inhibition inhibitor interferon interferon-gamma interleukin lesions leukemia leukocyte levels lymphocytes macrophages mechanisms mediated melanoma mice mitogenic molecules monoclonal antibodies monocytes mononuclear mRNA murine muscle Natl neutrophil normal Oncol osteoclast patients PDGF peripheral blood plasma platelet Proc production progenitor cells proliferation protein recombinant human regulation release renal rHu-TNF role serum soluble stimulate studies syndrome synthesis T-cell TGFB1 TGFẞ therapeutic therapy tion tissue TNFa toxicity transforming growth factor treatment tumor cells tumor necrosis factor vascular viral virus vitro vivo wound healing