The clinical and experimental effects of cytokines have been realized for a long time. The clinical effects of tumor necrosis factor were noted almost 100 years ago. The basic biological effects of interferons and the hemopoietic growth factors have been known for more than 20 years. Given the basis of modern molecular biotechniques, information concern­ ing the mediators of cellular interactions is expanding almost exponentially. New principles in the regulation of cell growth, microenvironment, immune response, and malignancy are being discoverd right now. New therapeutic options are becoming available and have, in some areas, already crossed the threshold of clinical application. However, the way forward might be more complicated than we are in a position to recognize today. Some of the first optimistic expectations have not yet been fulfilled. Nevertheless, we are experiencing a revolution in medicine. To contribute to this process and to stimulate scientific communi­ in this field, we have initiated the international symposia on cytokines cation in hemopoiesis, oncology and aids. Major contributions from the first sym­ posium are published in this book. We thank all the authors for their contri­ butions, particularly those from the Hannover Medical School, who have worked hard to realize the congress and prepare these proceedings. We also thank the pharmaceutical companies whose support made this book possible. Finally we thank Professors Deicher, Poliwoda, and Riehm, heads of the Departments of Hematology and Oncology, Immunology, and Pediatric Hematology and Oncology, respectively, who encouraged us and gave us their firm support.

Overview.- Colony Stimulating Factors:Past and Future.- Regulation of Hematopoietic Progenitor Cell Growth by Stimulating and Suppressing Cytokines.- Cytokine Interactions in Normal and Malignant Hematopoiesis.- Preclinical and In Vitro Data.- Colony Stimulating Factors in Normal Hematopoiesis.- Screening the Sensitivity of Hematopoietic Progenitor Cells to Different Growth Factors. Potential Importance in Therapy Trials with Colony Stimulating Factors.- Effect of Human Recombinant Interleukin-3 in Long-term Bone Marrow Culture.- Secretion of Colony-Stimulating Factor for Macrophages (M-CSF) and Granulocyte/Macrophages (GM-CSF) is Developmentally Regulated in Human Macrophages.- Expression of the M-CSF/CSF-1 Gene in Normal Human Alveolar Macrophages.- Surface Expression of Interleukin-2 Receptors and CD4 Molecules by Human Eosinophils is Induced by GM-CSF and IL-3.- Expression of Interleukin Receptors on Human Eosinophils, Basophils, and Mast Cells.- Chemiluminescene of Polymorphonuclear Leukocytes in Response to Interferons.- Glycolysis and Amino Acid Incorporation in IL-3-Dependent Cell Lines.- Fibroblast Colony Stimulating Activity of GM-CSF and IL-3 in Human Bone Marrow Cell Cultures.- Chromatin and DNA Methylation Changes of the Human Myeloperoxidase Gene During Myeloid Differentiation.- Retroviral-Mediated Transfer of Genes Encoding for Growth Factors into Human Hematopoietic Stem Cells.- Colony Stimulating Factors in Malignant Hematopoiesis.- Recruitment Therapy in Acute Myeloblasts Leukemia:A Different Approach to Improved Leukemia Treatment.- Effects of Hematopoietic Growth Factors on Myelodysplastic Syndrome Progenitors.- Combined Cytogenetic and Proliferation Studies of GM-CSF- Stimulated Bone Marrow Cells in Myelodysplasia and Acute Leukemia.- Recombinant Haemopoietic Factors (IL-3, IL-4, GM-CSF) Fail to Induce the Expression of Leucocyte Adhesion Receptors on Leukaemia Myeloid Colonies.- In Vitro Evaluation of Antiproliferative Activity of CCRF-CEM Supernatant on Lymphoid and Nonlymphoid Leukemic Cells.- TNF-?, IL-6, and Phorbol Ester but Not G-, M-, GM-CSF, IL-3, and IL-4 Induce Monocytic Differentiation and Modulate Expression of C-FOS, C-FMS, and C-MYC in the Human Monoblast Line THP-1.- In Vitro and In Vivo Inhibitory Effects of Interferon ? 2b on CML Granuloerythroid Precursors.- Several Cytokines Do Not Influence Activity of P210BCR-ABL Kinase in K562 Cells.- Colony Stimulating Factors in Nonhematopoietic Cells.- Target Cell Specifity of Hematopoietic Growth Factors.- Growth Factor-Dependent Stimulation of Primary Human Tumor Cells.- Stimulation of Colony Formation of Various Human Carcinoma Cell Lines by rhGM-CSF and rhIL-3.- Effects of Recombinant Cytokines on Clonogenic Cells from Primary Human Tumors.- Tumor Necrosis Factor and Interferon.- Mechanisms of TNF Action:Analysis of Receptor Structure and of Regulatory Circuits Controlling Receptor Expression and TNF-Production.- Synergism of Lymphotoxin and Interferon-? in the Growth Inhibition of Breast Cancer Cell Line MCF-7.- In Vitro Effect of Human Interferon-Gamma on Sister Chromatid Exchange Frequency and Proliferation of Cultured Human Amniotic Fluid Cells.- Tumor Necrosis Factor/Cachectin Production by B-Cell Chronic Lymphocytic Leukemia and Hairy Cell Leukemia Cells.- Interleukin-2.- Activation of Cytolytic Effector Cells.- Regulatory Effect of Recombinant Cytokines on NK Cell Differentiation from Early Marrow Precursors.- Human NK Clones Regulate B-cell Development by Release of IFN-? and TNF-?.- Expression of High Affinity IL-2 Receptors on a Hodgkin Cell Line.- Autologous Antileukemia Cytotoxicity Induced by PBL and BM Culture with rIL-2; Use in Autologous BMT for Inducing GVL?.- Interleukin-2-Induced Lymphokine-Activated Killer (LAK) Cells Against Human Leukemia:Improvement of Cytotoxicity by Combinations of Lymphokines or Cytokines.- Interleukin-2 (IL-2) in Acute Leukemia:In Vitro Studies and Possible Clinical Applications.- Other Effects and Factors.- Interleukin-l-? as a Modulator of Cytotoxic Drug Activity Against Human Cancer Cells.- Biological Properties of Human Interleukin-4.- Interleukin-6 (IL-6)/B Cell Stimulatory Factor 2-Dependent Growth of a Human IGA 2/K-Myeloma Cell Line.- Purification of a Mast Cell Growth-Enhancing Activity (MEA) Derived from a Murine Interleukin-2-Dependent, M1sa-Specific T Cell Line.- Mast Cell Growth-Enhancing Activity (MEA) is a Potent Inducer of Interleukin-6 Production in a Murine Interleukin-3- Dependent Mast Cell Line.- Monocyte-Conditioned Medium Factor as Auto-activation Signal for Monocyte Tumor Cytotoxicity.- A Lymphokine Distinct from IL-2 and IL-4 with Proliferative Activity for a CD4+ T Cell Clone is Preferentially Produced by TH2 Cells.- Leukoregulin Enhancement of Tumor Inhibitory Drug Uptake.- Increased Release of Cytokines from Human Peripheral Blood Mononuclear Cells by the ß-Galactoside-Specific Lectin from Clinically Applied Mistletoe Extract.- In Vitro Immunomodulatory Effects of the Thrombocytic Protein C 24.- Degree of 0- and N-Glycosylation of Lympnokines Released from A 23187-/TPA-Induced Lymphocytes Varies Differently with Culture Time.- Phorbol Myristate Acetate and Calcium Ionophore A23187 Induce Two Waves of Lymphokine mRNA Transcription in Stimulated Human Peripheral Blood Lymphocytes.- Comparison of the Engraftment Promoting Potential of High-Dose Cytostatic Agents in Allogeneic Bone Marrow Transplantation.- Clinical Data.- GM-CSF.- Hematopoietins as Adjuvant Therapy in Cancer Patients.- Effect of Chemotherapy Followed by GM-CSF for Acute Leukemias at Higher Age or After Relapse.- Growth Response of Acute Myeloid Leukemic Blasts to GM-CSF In Vitro and In Vivo-Observations in One Patient.- Recombinant Human Granulocyte-Macrophage Colony-stimulating Factor After Autologous Bone Marrow Transplantation.- Recombinant Human GM-CSF for Large-Scale Collection of Circulating Hematopoietic Progenitors in Cancer Patients Treated with High-Dose Cyclophosphamide.- Recombinant Human Granulocyte-Macrophage Colony-stimulating Factor for the Mobilization of Hemopoietic Progenitors Prior to Autologous Peripheral Blood Stem Cell Transplantation.- G-CSF.- Granulocyte Colony-stimulating Factor:Preclinical and Clinical Effects.- Biology and Clinical Applications of Human Granulocyte Colony-Stimulating Factor.- M-CSF.- In Vivo Evaluations of Recombinant Human Macrophage Colony-stimulating Factor.- Interleukin-3.- The In Vivo Effects of IL-3 and GM-CSF in Primates.- Erythropoietin.- IL-3-Enhanced EPO Effects in Subhuman Primates.- Use of Recombinant Human Erythropoietin after Bone Marrow Transplantation.- The Effect of Erythropoietin on Neutrophil Production from Fetal Hematopoietic Progenitors.- Response of Premature Anemic Infants to Subcutaneous Recombinant Erythropoietin.- Interferons.- Interferon-?2b as Therapy for Untreated and Pretreated Patients with Ph1 Positive Chronic Myelogenous Leukemia.- Interferon-?2b in Chronic Myelogenous Leukemia:Experience with Two Treatment Regimen.- Heterogeneous Progenitor Sensitivity to Various Cytokines in Patients with Myeloproliferative Disorders; Correlation of In Vitro Interferon-? Sensitivity with the Clinical Responsiveness to Recombinant Interferon-?.- Influence of Busulfan or Interferon-? Treatment on CFU-C from Bone Marrow and Peripheral Blood in Patients with CML in Chronic Phase.- Incomplete Stroma Formation by Bone Marrow from Chronic Myeloid Leukemia Patients Treated with Interferon.- Polymerase Chain Reaction for the Detection of Chimeric BCR/ABL mRNA in Patients with Chronic Myelogenous Leukemia (CML)-Detection of Minimal Residual Leukemic Cells After Bone Marrow Transplantation.- Interferon-? in the Treatment of Chronic Myeloproliferative Disorders with Thrombocytosis.- Recombinant Interferon-?, but not Interferon-?, is Effective Therapy for Essential Thrombocythemia.- The Role of Interferon-?2 (IFN-?2) in the Treatment of Low-Grade Non-Hodgkin's Lymphoma. Preliminary Results of a Randomized Study:IFN-?2 Plus Chlorambucil Versus Chlorambucil Alone.- T. Chisesi, L. Rancan, G. Capnist, G. Santini, A. Porcellini, R. Sertoli, A. Contu, V. Rizzoli, P. Coser, F. Benedetti.- Evaluation of Myelotoxic Effects in Non-Hodgkin's Lymphomas Treated with Interferon-? and Chlorambucil.- Response of Early Stage B-CLL to Interferon-?:2 Years Experience of a Pilot Study.- Successful Treatment of Angioimmunoblastic Lymphadenopathy (AIL) and B Cell Prolymphocytic Leukemia (B-PLL) with Interferon-?.- Interferon Treatment of Neuroendocrine Gut and Pancreatic Tumors.- Interferon-?2b in Patients with Endocrine Active Tumors.- Recombinant Interferon-?2b in Patients with Advanced Osteosarcoma after Aggressive Chemotherapy.- HIV-Associated Kaposi's Sarcoma Treated with Recombinant Interferon-?2b:Long-term Results.- Acute Effects of Recombinant IFN-? on White Blood Cell Counts and Lymphocyte Subsets in the Peripheral Blood of Cancer Patients.- Tumor Necrosis Factor.- Phase I Clinical Studies of Tumor Necrosis Factor in Patients with Advanced Cancer.- Increase of TNF-? Serum Levels in Major Transplant-Related Complications of Human Bone Marrow Transplantation-Association with Acute Graft-Versus-Host Disease and Activation of Host Macrophages.- Interleukin-2.- IL-2 and Cellular Therapy:Lymphokine-Activated Killer Cells and Tumor-Derived Activated Cells.- Sequential Bolus Administration of rIL-2 (RU 49637) in Treatment of Advanced Solid Malignancies.- rIL-2 Immunotherapy for 19 Children with Advanced Metastatic Neuroblastoma.- Interleukin-2 (IL-2) After Autologous Bone Marrow Transplantation (BMT):A Pilot Study of Late Administration, 2-3 Months Post ABMT.- IL-2 Treatment in a Patient with Stage IV Neuroblastoma After Allogeneic Bone Marrow Transplantation.- Regional Adoptive Immunotherapy for Hepatic Metastasis.- Adoptive Immunotherapy with IL-2 in 27 Patients with Metastatic Renal Cell Carcinoma.- Adoptive Immunotherapy of Advanced Cancer with LAK Cells and Different Dosages of Interleukin-2:Analysis of Lymphocyte Subpopulations.- Natural Interleukin-2 plus Lymphokine-Activated Killer Cells in Patients with Advanced Malignancy.- Evaluation of In Vivo Natural Killer and Lymphokine-Activated Killer Cell Activity in Patients Treated with High-Dose Interleukin-2 and Adoptive Transfer of Autologous LAK Cells.- Immunological Monitoring of Cancer Patients During a Phase I/II Clinical Trial of Natural Interleukin-2.- Antibodies to Interleukin-2 (IL-2) in Patients:Cross Reactivity with Different IL-2 Species.