Advances in Immunopharmacology (eBook)

Front Cover 1
Advances in Immunopharmacology 4
Copyright Page 5
Table of Contents 6
Part 1: Pharmacology of Immunotherapeuti Drugs and Immunotoxicology 12
Chapter 1. Immuno-enhancement and Drug Elimination Kinetics In Vivo 14
ABSTRACT 14
KEYWORDS 14
INTRODUCTION 14
HUMAN STUDIES 15
MOUSE STUDIES 16
REFERENCES 19
Chapter 2. Immunostimulants and Hepatic Drug Metabolism 22
ABSTRACT 22
KEYWORDS 22
INTRODUCTION 22
INFLUENCE OF C. PARVUM ON DRUG METABOLISM 23
RELATION OF ANTITUMOR ACTIVITY TO DEPRESSION OF DRUG METABOLISM 24
MECHANISM OF ACTION OF C. PARVUM 24
HUMORAL FACTORS 25
ACKNOWLEDGEMENT 25
REFERENCES 25
Chapter 3. Effects of Interferon Inducers and Viral Infection on the Metabolism of Drugs 28
ABSTRACT 28
KEYWORDS 28
ACKNOWLEDGEMENT 34
REFERENCES 34
Chapter 4. The Pharmacologic Properties of Various Forms of Interferon 36
ABSTRACT 36
KEYWORDS 36
INTRODUCTION 36
ISOLATION OF HuIFN-a SUBTYPES 37
PHARMACOKINETIC COMPARISONS OF HUMAN INTERFERON-ALPHA SUBTYPES 37
DISCUSSION 39
ACKNOWLEDGEMENT 39
REFERENCES 39
Chapter 5. The Pharmacokinetics of Immunoregulating Drugs: Immunopharmacokinetics 40
ABSTRACT 40
INTRODUCTION 40
PREDNISOLONE/PREDNISONE 41
AZATHI0PRINE/6-MERCAPT0PURINE 44
CYCLOPHOSPHAMIDE 45
IMMUNOSTIMULANTS 45
ACKNOWLEDGEMENT 46
REFERENCES 46
Chapter 6. Assessment of Immunotoxicity Induced by the Environmental Chemicals 2,3,7,8-Tetrachlorodibenzo-p-dioxin,Diethylstilbestrol and Benzo(a)pyrene 48
ABSTRACT 48
INTRODUCTION 48
MATERIALS AND METHODS 50
RESULTS 51
DISCUSSION 57
REFERENCES 59
Chapter 7. On the Heterogeneity of Immunotherapeutic Agents 62
ABSTRACT 62
KEYWORDS 62
INTRODUCTION 62
THE EFFECT OF CYTOTOXIC IMMUNODEPRESSANTS ON IMMUNOCYTE SUBPOPULATIONS 63
SOME OPEN PROBLEMS IN THE CHARACTERIZATION OF IMMUNOSTIMULANTS 68
ACKNOWLEDGMENT 73
REFERENCES 73
Part 2: Thymic Hormones 76
Chapter 8. A Multifaceted Role forThymosin and its Composite Peptides in T-Cell Regulation 78
ABSTRACT 78
KEYWORDS 78
INTRODUCTION 78
THYMOSIN AND ITS COMPONENT PEPTIDES 79
BIOLOGY OF THE THYMOSINS 81
CLINICAL TRIALS WITH THYMOSIN 83
SUMMARY AND PERSPECTIVES 84
ACKNOWLEDGEMENT 84
REFERENCES 84
Chapter 9. The Effect of the Serum Thymic Factor (FTS) on Suppressor T Cells 88
SUPPRESSION OF CELL-MEDIATED CYTOTOXICITY 89
INHIBITION OF SKIN GRAFT REJECTION (Bach, 1977 89
SUPPRESSION OF MOLONEY VIRUS INDUCED SARCOMA IMMUNE RESPONSES 89
SUPPRESSION OF ANTIBODY FORMATION IN NZB MICE 90
PREVENTION OF AUTOIMMUNITY IN NZB AND B/W MICE 90
IN VITRO RESTORATION OF SUPPRESSOR FUNCTION IN HUMAN LUPUS 91
DISCUSSION AND CONCLUSIONS 91
REFERENCES 91
Chapter 10. The Influence of Thymic Humoral Factor on Immunoproliferative Disorders andViral Infections in Humans 94
ABSTRACT 94
KEYWORDS 94
INTRODUCTION 94
MATERIALS AND METHODS 95
RESULTS AND DISCUSSION 97
CONCLUSIONS 99
REFERENCES 99
Part 3: Immunopharmacologic Approaches to Diseasesother than Cancer 100
Chapter 11. Virus Induced Immunomodulation 102
INTERACTION OF MICROBES WITH THE IMMUNE SYSTEM 102
FRIEND LEUKEMIA VIRUS INDUCED IMMUNOSUPPRESSION 103
DISCUSSION AND CONCLUSIONS 108
SUMMARY 110
REFERENCES 110
Chapter 12. Immunopharmacologic Approaches to Bacterial Infection 112
ABSTRACT 112
KEYWORDS 112
INTRODUCTION 112
ROLE OF GLUCOCORTICOIDS IN ENDOTOXIN-INDUCED SHOCK 112
ROLE OF IND0METHACIN ON THE PYROGENICITY AND ON IMMUN0STIMULATINGACTIVITIES OF SYNTHETIC ADJUVANT GLYC0PEPTIDES 113
ACKNOWLEDGEMENT 116
Chapter 13. Immunopotentiation in Experimental Viral Infections 120
ABSTRACT 120
KEYWORDS 120
INTRODUCTION 120
EXPERIMENTAL PROCEDURES 120
RESULTS 121
DISCUSSION 122
REFERENCES 124
Chapter 14. Immunologic Therapy of Viral Infections 126
ABSTRACT 126
KEYWORDS 127
INTRODUCTION 127
RESULTS 127
CLINICAL STUDIES 129
SSPE AND ACUTE VIRAL ENCEPHALITIS 134
CONCLUSIONS 135
REFERENCES 135
Chapter 15. Effects of Sex Hormones onSpontaneous Autoimmune Disease in NZB/NZW Hybrid Mice 138
ABSTRACT 138
KEYWORDS 138
INTRODUCTION 138
MATERIALS AND METHODS 139
RESULTS 141
DISCUSSION 146
ACKNOWLEDGMENTS 147
REFERENCES 147
Chapter 16. Immunopharmacologic Therapyof Connective Tissue Diseases 150
ABSTRACT 150
KEYWORDS 150
INTRODUCTION 150
CLINICAL ACTIVITY OF LEVAMISOLE IN R.A, 151
CLINICAL ACTIVITY OF THYMOPOIETIN (TP5) IN R.A. 155
IMMUNOREGULATORY EFFECT OF LEVAMISOLE AND THYMOPOIETIN 156
REFERENCES 158
Chapter 17. Immunopharmacologic Therapy of Immunodeficiency 160
ABSTRACT 160
KEYWORDS 160
TRANSFER FACTOR 160
LEVAMISOLE 164
REFERENCES 166
Part 4: Mechanisms ofChemotaxis Degranulationand Microbicidal Action 168
Chapter 18. Early Biochemical Responses of the Neutrophil to Chemoattractants 170
ABSTRACT 170
KEYWORDS 170
INTRODUCTION 170
THE TWO PROCESSES OF CALCIUM TRANSLOCATION IN THE NEUTROPHIL 171
INVOLVEMENT OF ARACHIDONIC ACID IN NEUTROPHIL FUNCTION 172
INTERRELATIONSHIP BETWEEN ARACHIDONIC ACID AND CALCIUM METABOLISM 173
REQUIREMENTS OF VARIOUS NEUTROPHIL RESPONSES FOR ARACHIDONIC ACID METABOLISM AND EXTRACELLULAR Ca2+ 173
ACKNOWLEDGEMENT 175
REFERENCES 175
Chapter 19. Complement-derived Chemotactic Factors 178
ABSTRACT 178
KEYWORDS 178
FORMATION OF HUMAN C5a AND C5a,des Arg 178
PHYSIOCHEMICAL CHARACTERIZATION OF HUMAN C5a AND C5a DERIVATIVES 179
BIOLOGICAL ACTIVITIES OF C5a 179
THE HUMAN NEUTROPHIL C5a RECEPTOR 181
ACKNOWLEDGEMENTS 184
REFERENCES 184
Chapter 20. Modification of Rat Polymorphonuclear Chemotaxis by Five Immunomodulators 186
ABSTRACT 186
KEYWORDS 186
INTRODUCTION 186
MATERIALS AND METHODS 187
RESULTS 187
DISCUSSION 191
ACKNOWLEDGEMENT 192
REFERENCES 192
Chapter 21. Use of Visual Analysis to Distinguish the Level of Actionof Drugs on Neutrophil Chemotaxis and Locomotion 194
ABSTRACT 194
KEY WORDS 194
INTRODUCTION 194
METHYLATION-INHIBITION MEDIA 195
ANAESTHETICS 196
COMPETITIVE ANTAGONISTS FOR f-MET PEPTIDES 197
CONCLUSIONS 198
ACKNOWLEDGEMENT 198
REFERENCES 198
Chapter 22. Receptors and Transductional Events in Leukocyte Chemotaxis 200
ABSTRACT 200
KEYWORDS 200
INTRODUCTION 200
ROLE OF MEMBRANE LIPIDS IN THE TRANSDUCTION OF CHEMOTACTIC SIGNALS 206
REFERENCES 207
Chapter 23. Mechanisms of Degranulation 208
ABSTRACT 208
KEYWORDS 208
INTRODUCTION 208
ROLE OF EXTRACELLULAR CATIONS 209
ROLE OF cAMP 211
ROLE OF PROSTAGLANDINS 212
MORPHOLOGY OF STIMULATED NEUTROPHILS 212
THE EFFECTS OF ANION TRANSPORT INHIBITORS 213
CONCLUSIONS 216
REFERENCES 216
Chapter 24. Oxygen-dependent CytotoxicActivity of Phagocytes 218
KEYWORDS 218
SUPEROXIDE ANION 218
HYDROGEN PEROXIDE 219
HYDROXYL RADICALS 221
SINGLET OXYGEN 222
ACKNOWLEDGEMENT 223
REFERENCES 223
Part 5: Cancer Immunopharmacology and Immunotherapy 226
Chapter 25. Immunological and Tumor Responses to Various Immunotherapeutic Agents 228
ABSTRACT 228
KEYWORDS 228
INTRODUCTION 228
MALEIC ANHYDRIDE DIVINYL ETHER COPOLYMER (MVE) 229
POLYINOSINIC-POLYCYTIDYLIC POLY-L-LYSINE (POLY ICLC) 232
INTERFERON AND MVE 235
REFERENCES 236
Chapter 26. Current Status of Human Cancer Immunotherapy 238
ABSTRACT 238
KEYWORDS 238
INTRODUCTION 238
REFERENCES 245
Chapter 27. Specific Active Immunization Against Cell Surface Antigens of Human Malignant Melanoma: Development of an Approach 246
INTRODUCTION 246
COMMENT 252
ACKNOWLEDGEMENT 252
REFERENCES 253
Part 6: Mechanisms ofI nflammatory and Allergic Processes 254
Chapter 28. Non-specific Inflammation and Host Resistance Against Pathogens 256
ABSTRACT 256
KEY WORDS 256
INTRODUCTION 256
INFLAMMATION INCREASES THE RESISTANCE OF MICE AGAINS TSCHISTOSOMA MANSONI 257
INFLAMMATION INCREASES THE RESISTANCE AGAINST CANDIDA ALBICANS AND PLASMODIUM BERGHEI 257
INFLAMMATION INCREASES THE RESISTANCE OF MICE AGAINST LISTERIA MONOCYTOGENES AND SALMONELLA TYPHIMURIUM 257
INFLAMMATION INCREASES THE RESISTANCE OF MICE AGAINST THE LEWIS CARCINOMA 258
KININS AND THEIR SPLIT-PRODUCTS ARE IMMUNOSTIMULANTS 258
CONCLUSIONS 258
ACKNOWLEDGEMENTS 259
REFERENCES 259
Chapter 29. Influence of an Acute Non-immunological Inflammation on Resistanceto Infection and Neoplasia 260
ABSTRACT 260
KEYWORDS 260
INTRODUCTION 260
DISCUSSION 266
ACKNOWLEDGMENTS 267
REFERENCES 268
Chapter 30. Immunopharmacology of Graft Rejection 270
REFERENCES 275
Chapter 31. Autacoids as Modulators of the Immune Process: A Possible Therapeutic Strategy 278
ABSTRACT 278
KEYWORDS 278
INTRODUCTION 279
AUTACOIDS AS MODIFIERS OF THE INFLAMMATORY AND IMMUNE RESPONSE 279
CONCLUSION 284
REFERENCES 284
Chapter 32. Immunopharmacologic Approaches to the Treatment of Allergy 288
ABSTRACT 288
KEYWORDS 288
INTRODUCTION 288
DEMONSTRATION OF A CIRCULATING" SUPPRESSIVE FACTOR OF ALLERGY" (SFA) ACTIVE IN SELECTIVELY INHIBITING IgE ANTIBODY RESPONSES 288
NEW APPROACHES T O IMMUNOTHERAPY OF IgE- MEDIATED ALLERGIC DISEASES 290
CONCLUSION 293
ACKNOWLEDGEMENT 294
REFERENCES 294
Part 7: Immune Testing of the Actions of Immunotherapeutic Agents 296
Chapter 33. Resistance Models for the Testing of Immunopotentiating Agents 298
ABSTRACT 298
INTRODUCTION 298
BACTERIAL INFECTIONS 299
FUNGAL INFECTIONS 300
PARASITIC INFESTATIONS 301
VIRAL INFECTIONS 302
TUMORS AND LEUKEMIAS 303
CONCLUSIONS 304
REFERENCES 304
Chapter 34. The Assessment of the Immunotoxicity of Xenobiotics Experience with Tetrachlorodibenzodioxin and Saccharin 306
ABSTRACT 306
INTRODUCTION 306
THE IMMUNOLOGICAL EFFECTS OF SACCHARIN 307
THE IMMUN0T0XIC0L0GY OF TCDD 312
ACKNOWLEDGEMENT 319
REFERENCES 319
Chapter 35. Attempt at Functional Classification of Chemically-Defined Immunomodulators 322
ABSTRACT 322
KEYWORDS 322
INTRODUCTION 322
RESULTS 323
ACKNOWLEDGMENTS 336
REFERENCES 336
Chapter 36. The Immunopharmacology of Immunotherapy: an Update 338
ABSTRACT 338
KEY WORDS 338
INTRODUCTION 338
ACTIONS OF AGENTS ON THE IMMUNE SYSTEM 339
HEMATOPOIESIS 340
LYMPHOCYTE DIFFERENTIATION 340
T CELL FUNCTIONS 341
B CELL FUNCTIONS 341
MACROPHAGE FUNCTIONS 342
MECHANISMS OF ACTION 344
THE NEED FOR A SCIENCE OF IMMUNOPHARMACOLOGY 346
CHARACTERISTICS OF THE AGENT 347
CHARACTERISTICS OF THE ANTIGENIC CHALLENGE 348
HOST CHARACTERISTICS IN IMMUNOTHERAPY 349
CONCLUSIONS 350
REFERENCES 350
Part 8: Prostaglandins and Macrophage Suppression 352
Chapter 37. Modulation of the PMN Leukocyte Component of Hypersensitivity Reactions by Lipoxygenase Products of Arachidonic Acid 354
ABSTRACT 354
KEYWORDS 354
LIPOXYGENASE PRODUCTS OF ARACHIDONIC ACID AS MEDIATORS OFPMN LEUKOCYTE FUNCTION 355
MODULATION OF THE GENERATION OF LIPOXYGENASE PRODUCTS OF ARACHIDONIC ACID BY HUMAN PMN LEUKOCYTES 358
ENDOGENOUS LIPOXYGENASE PRODUCTS OF ARACHIDONIC ACID AS FUNCTIONAL INTRACELLULAR CONSTITUENTS OF HUMAN PMN LEUKOCYTES 359
REFERENCES 362
Chapter 38. Arachidonic Acid and Related Fatty Acids in Leukocyte Modulation 366
KEYWORDS 366
Chapter 39. Generation of PGD2 and Releaseof Granule-associated Mediatorsby Mast Cells 368
REFERENCES 373
Chapter 40. Arachidonate and Metabolites in Mitogen Activation of Lymphocyte Guanylate Cyclase 376
ABSTRACT 376
KEYWORDS 376
INTRODUCTION 377
CYCLIC NUCLEOTIDE LEVELS 377
GUANYLATE CYCLASE 377
ACKNOWLEDGEMENTS 383
REFERENCES 383
Chapter 41. Prostaglandins and Macrophage Suppression 386
ABSTRACT 386
KEYWORDS 386
INTRODUCTION 386
METHODS 387
RESULTS 387
DISCUSSION 390
REFERENCES 391
Chapter 42. Prostaglandins in Lymphocyte Suppressor Mechanisms 394
ABSTRACT 394
KEYWORDS 394
INTRODUCTION 394
PG PRODUCTION BY IMMUNOCOMPETENT CELLS 395
PG PRODUCTION AND CONTROL OF MITOGEN INDUCED LYMPHOCYTE ACTIVATION 395
REFERENCES 398
Part 9: Selected Topics 400
Chapter 43. Immunopharmacologic Approaches to Delineation ofthe Mechanism of Cell-Mediated Cytotoxicity Using Cytotoxic T Cell Clones 402
ABSTRACT 402
KEYWORDS 402
INTRODUCTION 402
RESULTS AND DISCUSSION 403
ACKNOWLEDGEMENTS 406
REFERENCES 406
Chapter 44. Mechanism of Action of Soluble Immune Response Suppressor (SIRS) 408
ABSTRACT 408
KEYWORDS 408
INTRODUCTION 408
MECHANISM OF ACTION 409
PROPERTIES OF SIRS 409
MECHANISM OF SIRS ACTION 410
MECHANISMS OF M.-SF ACTION 411
PROPERTIES OF M.-SF 412
MECHANISMS OF PRODUCTION OF M.-SF 413
CONCLUSION 414
ACKNOWLEDGEMENTS 415
REFERENCES 415
Chapter 45. The Diagnostic and Therapeutic Uses of Monoclonal Antibodies 416
PRINCIPLE 416
COMPARISON BETWEEN CONVENTIONAL AND MONOCLONAL REAGENTS 416
MONOCLONAL ANTIBODIES IN MEDICINE 417
ACKNOWLEDGEMENTS 419
REFERENCES 420
Chapter 46. New Approaches to the Therapyof Allergic Diseases 422
ABSTRACT 422
KEYWORDS 422
INTRODUCTION 422
THE MECHANISM OF MEDIATOR RELEASE 423
OTHER MEDIATORS OF ANAPHYLAXIS 426
MEDIATOR INTERACTIONS 427
REFERENCES 428
Chapter 47. Lymphocyte Activating Propertyof Human Leukocytic Pyrogen 430
ABSTRACT 430
KEYWORDS 430
INTRODUCTION 430
MATERIALS AND METHODS 431
RESULTS 431
DISCUSSION 434
ACKNOWLEDGEMENT 435
REFERENCES 435
Chapter 48. The Central Nervous Systemand Immune Responses: Conditioned Immunopharmacologic Effects 438
ABSTRACT 438
KEYWORDS 438
INTRODUCTION 438
BACKGROUND 439
CONDITIONED IMMUNOSUPPRESSION 440
DISCUSSION 443
ACKNOWLEDGMENTS 445
REFERENCES 445
Chapter 49. Immunopharmacology of Schistosomiasis 446
IMMUNOPATHOLOGY 447
IMMUNITY, SPECIFIC AND NON-SPECIFIC 449
REFERENCES 450
Part 10: Therapy Communication Sessions 452
Chapter 50. Mycobacteria, G. Parvum and Related Substances 454
BCG AND RELATED BACTERIAL FRACTIONS 455
ANAEROBIC CORYNEFORMS 456
STREPTOCOCCUS PREPARATIONS 457
NEURAMINIDASE 457
Chapter 51. Interferon Inducers 458
Chapter 52. Immunopotentiators I 462
1. BESTATIN 463
2. LEVAMISOLE 463
3. DTC 464
4. SA 96 466
5. F 1686 466
CLOSING COMMENTS 466
Chapter 53. Immunopotentiators III soprinosine, NPT 15392 and Azimexone: Modulators of Lymphocyte and Macrophage Development and Function 468
ABSTRACT 469
KEYWORDS 469
ISOPRINOSINE 469
EFFECTS OF ISOPRINOSINE ON IMMUNE FUNCTION IN VITRO 469
EFFECTS OF ISOPRINOSINE ON IMMUNE FUNCTION IN VIVO 471
EFFECTS OF NPT 15392 ON IMMUNE FUNCTION IN VITRO 474
EFFECT OF NPT 15392 ON IMMUNE FUNCTION IN VIVO 475
AZIMEXONE 476
EFFECTS OF AZIMEXONE IN VITRO 476
EFFECTS OF AZIMEXONE IN VIVO 477
Chapter 54. Interferon 480
Chapter 55. Polysaccharides and Related Substances I 488
Chapter 56. Polysaccharides and Related Substances II 496
Chapter 57. New Immunosuppressive Agents and Approaches 502
Chapter 58. New Host Modifying Drugs 506
Chapter 59. Muramyl Dipeptide Immunoadjuvants 510
Chapter 60. Summary and Conclusions of the Therapy and Communication Session: Lymphokine and Transfer Factor 518
Author Index 524