Cytokines and the Brain (eBook)

Cover 1
TOC$Table of Contents 6
Foreword 10
Preface 16
In Memoriam – Christopher P. Phelps, PhD 18
Obituary 20
List of Contributors 28
Part I. History 34
CH$Chapter 1 The History of Neuroimmune Biology 36
ABSTRACT 36
1. INTRODUCTION 37
2. NEURAL REGULATION OF ALLERGY AND ASTHMA 38
3. NEUROENDOCRINE–IMMUNE INTERACTION 41
4. NEUROIMMUNE REGULATON IN HIGHER ORGANISMS 42
5. CONCLUDING REMARKS 43
REFERENCES 44
Part II. Cytokines in the Brain 52
Section A. Cytokines, their Receptors and Signal Transduction in the Brain 52
CH$Chapter 2 Cytokine Receptors in the Brain 54
ABSTRACT 54
1. BASAL AND INDUCED LEVELS OF CYTOKINES IN THE BRAIN 54
2. DISTRIBUTION OF CYTOKINE RECEPTORS 55
3. SIGNALING THROUGH CYTOKINE RECEPTORS IN THE BRAIN 57
4. FUNCTIONAL ROLES OF CYTOKINE AND CYTOKINE RECEPTORS IN THE BRAIN 59
5. CONCLUSIONS 65
REFERENCES 65
CH$Chapter 3 Interleukin-1 and Corticotropin-Releasing Factor Receptors in the Hypothalamic–Pituitary–Adrenal Axis 72
ABSTRACT 72
1. INTRODUCTION 72
2. LOCALIZATION OF IL-1 RECEPTORS IN HYPOTHALAMUS 73
3. LOCALIZATION OF IL-1 RECEPTORS IN PITUITARY 74
4. MODULATION OF IL-1 RECEPTORS BY CRF IN THE HPA AXIS 75
5. SUMMARY AND CONCLUSIONS 82
ACKNOWLEDGEMENTS 83
REFERENCES 83
CH$Chapter 4 Brain Interleukin-1ß Expression and Action in the Absence of Neuropathology 88
ABSTRACT 88
1. INTRODUCTION 88
2. BRAIN IL-1ß EXPRESSION AND ACTION: CHARACTERISTICS AND PITFALLS 89
3. BRAIN IL-1ß AND RECEPTOR EXPRESSION DURING DEVELOPMENT 92
4. CONSTITUTIVE BRAIN EXPRESSION OF IL-1ß AND ITS RECEPTORS 93
5. ROLE OF CONSTITUTIVE BRAIN IL-1B IN LEARNING AND SLEEP REGULATION 95
6. BRAIN IL-1ß PRODUCTION AND ACTION DURING STRESS 97
7. BRAIN IL-1ß INDUCTION AND ACTION DURING THE ACUTE PHASE RESPONSE 99
8. CONCLUSIONS 100
REFERENCES 100
CH$Chapter 5 Interleukin-1ß Signal Transduction via the Sphingomyelin Pathway in Brain Cells 112
ABSTRACT 112
1. INTRODUCTION 112
2. THE SPHINGOMYELIN PATHWAY OF INTERLEUKIN-1ß SIGNALING 114
3. ACTIVATION OF NEUTRAL SPHINGOMYELINASE AND THE NECESSITY OF INTERLEUKIN-1ß RECEPTOR TYPE I FOR SIGNALING NERVE CELLS 115
4. CHANGES IN NEUTRAL SPHINGOMYELINASE ACTIVITY IN MEMBRANES OF NERVE AND IMMUNE-COMPETENT CELLS UNDER STRESS 117
5. MODULATORY EFFECTS OF GLUCOCORTICOID HORMONES AND SHORT PEPTIDES ON THE ACTIVITY OF NEUTRAL SPHINGOMYELINASE 118
6. INTERLEUKIN-1ß SIGNALING THROUGH THE SPHINGOMYELIN PATHWAY IN ASTROCYTES 119
7. CONCLUSIONS 120
ACKNOWLEDGMENTS 120
REFERENCES 120
CH$Chapter 6 Blood–Brain Barrier Transport of Cytokines 126
ABSTRACT 126
1. INTRODUCTION 126
2. BLOOD-TO-BRAIN TRANSPORT 127
3. BRAIN-TO-BLOOD TRANSPORT 129
4. BEHAVIORAL EFFECTS OF CYTOKINES AND THE BBB 129
5. SPECIES SPECIFICITY 131
6. PHYSIOLOGICAL ALTERATIONS 131
7. PATHOLOGICAL ALTERATIONS IN TRANSPORT 132
8. OTHER CYTOKINE–BBB INTERACTIONS 132
9. CONCLUSIONS 133
ACKNOWLEDGMENTS 133
REFERENCES 133
Section B. Cytokines in Brain Physiology 142
CH$Chapter 7 Cytokines in Synaptic Function 144
ABSTRACT 144
1. INTRODUCTION 145
2. BASIC CONCEPTS AND PRINCIPLES OF SYNAPTIC TRANSMISSION 146
3. TUMOR NECROSIS FACTOR-a 148
4. INTERLEUKINS 151
5. INTERFERONS 153
6. CHEMOKINES 155
7. IMPLICATIONS FOR DISEASES 157
8. G-PROTEINS 160
9. CONCLUDING REMARKS 161
ACKNOWLEDGEMENTS 162
REFERENCES 162
CH$Chapter 8 Interleukin-2 as a Neuroregulatory Cytokine 178
ABSTRACT 178
1. INTRODUCTION 178
2. IL-2 AND IL-15: TWO CYTOKINES SHARING A HETEROMERIC RECEPTOR COMPLEX 179
3. EXPRESSION OF IL-2, IL-15, AND THEIR RECEPTORS IN THE CNS 182
4. EFFECTS ON NEURAL CELL GROWTH, SURVIVAL, AND DIFFERENTIATION 184
5. EFFECTS ON THE FIRING ACTIVITY AND THE RELEASE PROPERTIES OF NEURONS 186
6. NEUROPATHOLOGICAL AND THERAPEUTIC IMPLICATIONS 189
ACKNOWLEDGMENT 190
REFERENCES 190
CH$Chapter 9 Cytokines and Extracellular Matrix Remodeling in the Central Nervous System 200
ABSTRACT 200
1. INTRODUCTION 200
2. ECM LOCALIZATION IN BRAIN 201
3. CNS-ECM MAIN MOLECULAR CLASSES AND COMPOSITION 207
4. FUNCTIONAL INVOLVEMENT OF ECM MOLECULES IN SYNAPTIC PLASTICITY 211
5. ECM–CYTOKINES AND GROWTH FACTORS IN CNS INJURY 215
6. CONCLUSIONS AND FUTURE DIRECTIONS 221
REFERENCES 221
CH$Chapter 10 Acidic Fibroblast Growth Factor, a Satiety Substance, with Diverse Physiological Significance 232
ABSTRACT 232
1. INCREASE IN FIBROBLAST GROWTH FACTOR IN CEREBROSPINAL FLUID AFTER FEEDING 232
2. EFFECTS OF ANTIBODIES TO AFGF AND BFGF ON FOOD INTAKE 233
3. FGF EFFECTS ON LHA AND VMH NEURONS 234
4. SOURCE OF aFGF IN THE BRAIN 234
5. GLUCOSE SENSOR OF A NEW TYPE IN THE BRAIN 234
6. aFGF AND MEMORY FACILITATION 235
7. PERSPECTIVES 236
8. ACTIVATION OF AFGF ON HYPOTHALAMIC–PITUITARY–ADRENOCORTICAL AXIS 238
9. EFFECTS OF AFGF AND ITS FRAGMENTS ON PHAGOCYTOSIS IN MOUSE PERITONEAL MACROPHAGES 241
10. CONCLUSIONS 242
REFERENCES 243
CH$Chapter 11 Cytokines and Sleep 246
ABSTRACT 246
1. INTRODUCTION 246
2. SLEEP 247
3. CYTOKINES AND SLEEP 249
4. ACTIVITY-DEPENDENT EXPRESSION OF CYTOKINE SRSs 256
5. BRAIN ORGANIZATION OF SLEEP 257
6. ROLE OF CYTOKINES IN EXPERIMENTAL EVIDENCE FOR THE THEORY 259
7. CONCLUSIONS 260
ACKNOWLEDGMENTS 260
REFERENCES 260
Section C. Chemokines in the Brain 274
CH$Chapter 12 Chemokines, their Receptors and Significance in Brain Function 276
ABSTRACT 276
1. INTRODUCTION 276
2. STRUCTURE AND CLASSIFICATION OF CHEMOKINES AND CHEMOKINE RECEPTORS 277
3. SIGNAL TRANSDUCTION 281
4. EXPRESSION OF CHEMOKINE AND THEIR RECEPTORS IN THE BRAIN: CELLULAR LOCALIZATION AND PHYSIOLOGICAL ROLES 284
5. CHEMOKINES IN BRAIN DEVELOPMENT 287
6. CHEMOKINE AND CHEMOKINE RECEPTOR INVOLVEMENT IN BRAIN PATHOLOGIES 290
REFERENCES 295
Part III. Immune Response in the Brain 308
CH$Chapter 13 Immune and Inflammatory Responses in the Central Nervous System: Modulation by Astrocytes 310
ABSTRACT 310
1. INTRODUCTION 310
2. ASTROCYTES IN THE NORMAL BRAIN 311
3. REACTIVE ASTROGLIOSIS 312
4. ASTROCYTES AND CYTOKINES 314
5. ASTROCYTES AND OXIDATIVE STRESS 316
ACKNOWLEDGMENTS 317
REFERENCES 317
CH$Chapter 14 Immune Response in the Brain: Glial Response and Cytokine Production 322
ABSTRACT 322
1. INTRODUCTION 322
2. GLIAL RESPONSE TO INTERACT WITH IMMUNE CELLS 323
3. CYTOKINE PRODUCTION AND EXPRESSION OF RECEPTORS FOR CYTOKINES IN GLIA CELLS 324
4. CYTOKINE NETWORKS IN THE CENTRAL NERVOUS SYSTEM 326
5. CYTOKINES IN THE CENTRAL NERVOUS SYSTEM PATHOLOGIES 328
REFERENCES 331
Part IV. Cytokines in Pathophysiological Brain Responses 338
Section A. Brain–Immune Interaction 338
CH$Chapter 15 Lymphocytes and Adrenergic Sympathetic Nerves: The Role of Cytokines 340
ABSTRACT 340
ABBREVIATIONS 340
1. INTRODUCTION 341
2. INNERVATION OF LYMPHOID ORGANS 341
3. EXPRESSION OF ARS ON LYMPHOCYTES 342
4. EFFECT OF ADRENERGIC STIMULATION ON T LYMPHOCYTES 343
5. EFFECT OF ADRENERGIC STIMULATION ON B LYMPHOCYTES 344
6. EFFECT OF ADRENERGIC STIMULATION ON NATURAL KILLER CELLS 345
7. EFFECT OF DEPLETION OF NORADRENERGIC INNERVATION ON LYMPHOCYTES 346
8. EFFECTS OF CYTOKINES ON THE SYMPATHETIC NERVOUS SYSTEM 347
9. CATECHOLAMINE SYNTHESIS BY LYMPHOCYTES 354
10. CONCLUSIONS 356
REFERENCES 357
CH$Chapter 16 Cytokines in Neural Signaling to the Brain 370
ABSTRACT 370
1. INTRODUCTION 370
2. CRANIAL NERVE VISCEROSENSORY PATHWAYS: NEURAL SURVEILLANCE OF PATHOGEN INTERFACES 371
3. CYTOKINES IN SPINAL AND TRIGEMINAL NERVES AND PAIN MODULATION 376
4. CENTRAL PROJECTIONS OF CYTOKINE-RESPONSIVE NERVES: INTERFACE WITH BRAIN REGIONS SUBSERVING SICKNESS RESPONSES 377
5. PERSPECTIVES 378
ACKNOWLEDGMENTS 380
REFERENCES 380
CH$Chapter 17 Interleukin-2 Gene Expression in Central Nervous System Cells after Stress and Antigen Application 386
ABSTRACT 386
1. INTRODUCTION 386
2. INTERLEUKIN-2 AS AN ENDOGENOUS CYTOKINE OF CENTRAL NERVOUS SYSTEM 387
3. INTERLEUKIN-2 GENE EXPRESSION IN BRAIN CELLS OF RATS EXPOSED TO STRESS 388
4. EXPRESSION OF C-FOS AND INTERLEUKIN-2 GENES IN BRAIN CELLS AFTER INJECTION OF ANTIGEN 390
5. EXPRESSION OF C-FOS AND INTERLEUKIN-2 GENES BY BRAIN CELLS OF RATS AFTER THE APPLICATION OF AN IMMUNOMODULATING PEPTIDES 393
6. THE POSSIBLE PATHWAYS OF TRANSMISSION OF INTERLEUKIN-2 SIGNALS INTO CENTRAL NERVOUS SYSTEM CELLS 395
7. CONCLUSION 396
ACKNOWLEDGMENTS 397
REFERENCES 397
CH$Chapter 18 Sex Hormones and Cytokines in Central Nervous System Pathology and Repair 406
ABSTRACT 406
1. INTRODUCTION 406
2. EFFECTS OF STERIOD HORMONES IN CENTRAL NERVOUS SYSTEM INFLAMMATION 407
3. REGULATION OF INFLAMMATORY MEDIATORS BY SEX STEROIDS 409
4. STEROID HORMONES AND CENTRAL NERVOUS SYSTEM REPAIR 410
5. NEUROSTEROIDOGENESIS 413
6. CONCLUSION 415
REFERENCES 415
CH$Chapter 19 Involvement of Brain Cytokines in Stress-induced Immunosuppression 424
ABSTRACT 424
1. INTRODUCTION 424
2. CYTOKINE EXPRESSION IN THE BRAIN DURING INFLAMMATORY STRESS 425
3. IMMUNOSUPPRESSION INDUCED BY BRAIN CYTOKINES 425
4. ROLE OF BRAIN CYTOKINES IN THE IMMOBILIZATION-INDUCED IMMUNOSUPPRESSION 428
5. CONCLUSION 430
ACKNOWLEDGMENTS 431
REFERENCES 431
CH$Chapter 20 Neuroprotective Effects of Inflammation in the Nervous System 436
ABSTRACT 436
1. INTRODUCTION 436
2. THE PROTECTIVE ROLE OF MACROPHAGES 438
3. THE PROTECTIVE ROLE OF T CELLS 440
4. ANTIBODIES AS MEDIATORS OF CENTRAL NERVOUS SYSTEM REPAIR 442
5. THE DUAL ROLE OF PROINFLAMMATORY CYTOKINES 443
6. SECRETION OF NEUROTROPHIC FACTORS BY INFLAMMATORY CELLS 447
7. CONCLUDING REMARKS 450
ACKNOWLEDGMENTS 451
REFERENCES 451
Part V. Disease 466
CH$Chapter 21 Brain Response to Endotoxin 468
ABSTRACT 468
1. INTRODUCTION 468
2. LIPOPOLYSACCHARIDE-INDUCED SIGNALING PATHWAYS 469
3. THE ACUTE INFLAMMATORY RESPONSE 470
4. EPITHELIAL AND ENDOTHELIAL BARRIERS 472
5. BARRIER RESPONSES TO LIPOPOLYSACCHARIDE 474
6. SUMMARY AND CONCLUSIONS 483
ACKNOWLEDGMENTS 484
REFERENCES 484
CH$Chapter 22 Cytokines in Demyelinating Diseases 488
ABSTRACT 488
1. CYTOKINE EXPRESSION DURING MULTIPLE SCLEROSIS AND EXPERIMENTAL AUTOIMMUNE ENCEPHALITIS 489
2. CONCLUSIONS 508
REFERENCES 509
CH$Chapter 23 The Cytokines and Depression Hypothesis: An Evaluation 518
ABSTRACT 518
1. INTRODUCTION 518
2. ORIGINS OF THE CYTOKINE HYPOTHESIS OF DEPRESSION 519
3. EXPERIMENTAL EVIDENCE FOR THE CYTOKINE HYPOTHESIS OF DEPRESSION 520
4. ARE SYMPTOMS OF DEPRESSION OBSERVED IN SICK ANIMALS? 524
5. THE POTENTIAL ROLE IN SICKNESS BEHAVIOR OF CYTOKINES IN THE BRAIN 524
6. EFFECTS OF ANTIDEPRESSANT TREATMENTS ON SICKNESS BEHAVIOR 527
7. CYTOKINE ACTIVATION OF THE HYPOTHALAMIC–PITUITARY–ADRENOCORTICAL AXIS: RELATIONSHIP TO DEPRESSION 527
8. CYTOKINES AND BRAIN CATECHOLAMINES 528
9. THE VALUE OF CYTOKINE-INDUCED SICKNESS BEHAVIOR AS A MODEL FOR THE STUDY OF DEPRESSION 530
10. CONCLUSIONS 531
ACKNOWLEDGMENTS 532
REFERENCES 532
CH$Chapter 24 Clinical Relevance: Cytokines in Alzheimer’s Disease 540
ABSTRACT 540
1. INTRODUCTION 540
2. CYTOKINES 542
3. CYTOKINE RECEPTORS 543
4. INTRACELLULAR SIGNALING AND CYTOKINES 543
5. NEUROTRANSMITTERS AND CYTOKINES 544
6. OXIDATIVE FREE RADICALS, AGING, AND INFLAMMATION IN THE CENTRAL NERVOUS SYSTEM 545
7. NEUROPATHOPHYSIOLOGY OF ALZHEIMER’S DISEASE 546
8. SPECULATIONS ON THE CAUSE, TREATMENT, AND PREVENTION OF ALZHEIMER’S DISEASE 552
REFERENCES 554
Part VI. Cytokines and Behavior 560
CH$Chapter 25 Cytokines and Immune-Related Behaviors 562
ABSTRACT 562
1. INTRODUCTION 562
2. HOST RESPONSE TO INFECTION AND INFLAMMATION 563
3. NONSPECIFIC SYMPTOMS AS ADAPTIVE RESPONSES TO INFECTION AND INFLAMMATION 565
4. SICKNESS AS A MOTIVATIONAL STATE: THE FLEXIBILITY OF IMMUNE-RELATED BEHAVIORS 567
5. SICKNESS AND INFORMATION PROCESSING: THE SICK ANIMAL IN ITS ENVIRONMENT 569
6. EVOLUTIONARY ROOTS OF IMMUNE-RELATED BEHAVIORS 573
7. CONCLUSIONS 574
REFERENCES 575
CH$Chapter 26 The Production and Effects of Cytokines Depend on Brain Lateralization 582
ABSTRACT 582
1. INTRODUCTION 582
2. EFFECTS OF UNILATERAL BRAIN LESIONS ON IMMUNITY AND CYTOKINE PRODUCTION 584
3. EFFECTS OF FUNCTIONAL LATERALIZATION ON IMMUNITY AND CYTOKINE PRODUCTION 585
4. INFLUENCE OF LATERALIZATION ON THE EFFECTS OF CYTOKINES 588
5. BRAIN–IMMUNE PATHWAYS INVOLVED IN LATERALIZED CONTROL OF CYTOKINE PRODUCTION 588
6. CONCLUSION AND PERSPECTIVES 590
REFERENCES 591
Part VII. Conclusions 598
CH$Chapter 27 Concluding Remarks 600
IDX$Subject Index 604