CONTENTS

Cover

Title Page

Preface

Chapter 1: Inflammation through the Ages: A Historical Perspective

1.1 Introduction
1.2 The First Treatments
1.3 The Definitions
1.4 Fever
1.5 Phagocytosis
1.6 Diapedesis
1.7 Chemotactism
1.8 Infection and Inflammation
1.9 Usefulness of Inflammation for Adaptive Immune Response
1.10 Mediators of Inflammation
References

Part One: Inducers and Sensors of Inflammation

Chapter 2: Pathogen-associated Molecular Patterns
1. 2.1 Definition
2. 2.2 Endotoxin
3. 2.3 Other Bacterial PAMPs
4. 2.4 Viral PAMPs
5. 2.5 Parasitic PAMPs
6. 2.6 Fungal PAMPs
7. 2.7 Synergy
8. References
Chapter 3: Damage-associated Molecular Patterns
1. 3.1 Definition
2. 3.2 Necrosis versus Apoptosis
3. 3.3 Receptors of Danger Signals
4. 3.4 Main DAMPs
5. References
Chapter 4: Bacterial Toxins
1. 4.1. Introduction
2. 4.2 Toxins Modulating the Activity of Inflammatory Caspases and Inflammasomes
3. 4.3 Toxins Modulating the Intracellular cAMP Levels
4. 4.4 Toxins Modulating MAPK Signaling
5. 4.5 Toxins Affecting Host Cell Motility
6. 4.6 Toxins Blocking Protein Synthesis or Protein Folding
7. 4.7 Conclusions
8. References
Chapter 5: Venoms
1. 5.1 Introduction
2. 5.2 Inflammation Induced by Snake Venoms
3. 5.3 Inflammation Induced by Scorpion Venoms
4. 5.4 Inflammation Induced by Spider Venoms
5. 5.5 Inflammation Induced by Venoms of Bees, Vespids, and Ants
6. 5.6 Conclusions
7. References
Chapter 6: Hypoxia as an Inducer of Inflammation
1. 6.1 Introduction
2. 6.2 Oxygen Sensing
3. 6.3 Mitochondrial Oxygen Sensing
4. 6.4 The Role of Transcription Factors
5. 6.5 The Warburg Effect
6. 6.6 Acute versus Chronic Hypoxia
7. 6.7 Inflammasome Activation
8. 6.8 Summary and Conclusions
9. References
Chapter 7: Vaccine Adjuvants
1. 7.1 Introduction
2. 7.2 Adjuvants Approved for Human Use
3. 7.3 Aluminum Compounds: The Gold Standard
4. 7.4 AS04
5. 7.5 Calcium Phosphate
6. 7.6 Emulsions
7. 7.7 Nano/microparticles Including Liposomes and Virosomes
8. 7.8 Immune Stimulating Complexes
9. 7.9 Cytokines
10. 7.10 Adjuvants that Target Toll-like Receptors
11. 7.11 Adjuvant Combinations
12. 7.12 Future Directions
13. References
Chapter 8: Pattern Recognition Receptors
1. 8.1 Introduction
2. 8.2 Toll-like Receptors
3. 8.3 C-type Lectin Receptors
4. 8.4 Natural Killer Gene Complex-associated CLRs
5. 8.5 RIG-1-like Receptors
6. 8.6 NOD-like Receptors
7. 8.7 DNA-sensing Molecules
8. 8.8 Conclusions
9. Acknowledgments
10. References

Part Two: Inflammatory Cells

Chapter 9: Monocytes and Macrophages
1. 9.1 Introduction
2. 9.2 Origin and Differentiation
3. 9.3 Activation and Polarization
4. 9.4 Functions
5. 9.5 Molecular Pathways and Mechanisms Regulating Response
6. 9.6 Conclusions
7. Acknowledgment
8. References
Chapter 10: Neutrophils
1. 10.1 Characteristics
2. 10.2 Hematopoiesis
3. 10.3 Adhesion and Migration
4. 10.4 Phagocytosis and Degranulation
5. 10.5 Cytokine Synthesis
6. 10.6 Neutrophil Apoptosis
7. 10.7 Neutrophils in Pathology
8. 10.8 Conclusions
9. References
Chapter 11: Mast Cells: Master Drivers of Immune Responses against Pathogens
1. 11.1 Introduction
2. 11.2 Biology of Mast Cells
3. 11.3 Role of Mast Cells in Immune Surveillance
4. 11.4 Mast Cells in Innate Immunity
5. 11.5 Mast Cells in Adaptive Immunity
6. 11.6 Enhancement of Immunity by Boosting Mast Cell Activity
7. 11.7 Potentially Detrimental Roles of Mast Cell Activation during Immune Responses
8. 11.8 Concluding Remarks
9. Acknowledgments
10. References
Chapter 12: Dendritic Cells in Inflammatory Disease
1. 12.1 What Defines a Dendritic Cell?
2. 12.2 Dendritic Cell Subsets
3. 12.3 Dendritic Cells and T-cell Polarization
4. 12.4 Dendritic Cells in Allergic Inflammation
5. 12.5 Inflammatory DCs' Role in Human Allergy
6. 12.6 Dendritic Cells in Autoimmune Inflammatory Disease
7. 12.7 Conclusions
8. References
Chapter 13: Roles for NK Cells and ILC1 in Inflammation and Infection
1. 13.1 Introduction
2. 13.2 Distinguishing Group 1 ILC and NK Cells
3. 13.3 NK Cell and ILC1 Activating and Inhibitory Receptors
4. 13.4 Evidence for Distinct Subsets of NK Cells and ILC1
5. 13.5 Effector Functions of NK Cells and ILC1
6. 13.6 NK Cells and Group 1 ILCs in Inflammation and Infection
7. 13.7 NK Cell and ILC1 Memory
8. 13.8 Concluding Remarks: NK and ILC1 as Partners in a Type 1 Network
9. References
Chapter 14: Group 2 and 3 Innate Lymphoid Cells: New Actors in Immunity and Inflammation
1. 14.1 ILCs: A New Family of Innate Effector Cells
2. 14.2 ILC2 and ILC3 Heterogeneity and Homeostasis
3. 14.3 ILC2 in Acute and Chronic Inflammation
4. 14.4 ILC3 in Acute and Chronic Inflammation
5. 14.5 Therapeutically Harnessing ILC2 and ILC3
6. 14.6 Concluding Remarks
7. References
Chapter 15: Th9 Cells: From the Bench to the Bedside and Back Again
1. 15.1 The History of T Helper Cells
2. 15.2 Introduction to Th9 Cells
3. 15.3 Th9 Cells in Disease: The Helpful and Unhelpful
4. 15.4 Targeting Th9 Cells Therapeutically
5. 15.5 Summary and Future Directions
6. References
Chapter 16: Th17 Cells
1. 16.1 Introduction
2. 16.2 Differentiation of Th17 Cells
3. 16.3 Cytokines and Chemokines Related to Th17 Cells
4. 16.4 Th17 and Inflammatory Diseases
5. 16.5 Mechanisms in Chronic Inflammation
6. 16.6 Plasticity of Th17 Cells
7. 16.7 Clinical Targeting of Th17 Cells
8. 16.8 Conclusions
9. Acknowledgment
10. References
Chapter 17: Platelets
1. 17.1 Introduction
2. 17.2 Expression of Toll-like Receptors
3. 17.3 Interactions between Platelets and Bacteria
4. 17.4 Interactions between Platelets and White Blood Cells
5. 17.5 Platelet Integrins
6. 17.6 Role of Platelets in Immune Responses
7. 17.7 Platelets and Inflammatory Disorders
8. 17.8 Malaria
9. 17.9 Systemic Lupus Erythematosus
10. 17.10 Conclusions
11. References
Chapter 18: Epithelial Cells
1. 18.1 Introduction
2. 18.2 The Intestinal Epithelium: An Archetypal Epithelial Barrier
3. 18.3 Choosing a Cell Fate: The Absorptive Lineage
4. 18.4 Choosing a Cell Fate: The Secretory Lineage
5. 18.5 The Epithelium: The Sum is Greater than its Parts
6. 18.6 Epithelial Homeostasis: Maintaining the Balance
7. 18.7 Concluding Remarks
8. References
Chapter 19: Inflammation: The Role of Endothelial Cells
1. 19.1 Introduction
2. 19.2 Vasomotor Dysfunction
3. 19.3 Conclusions
4. References

Part Three: Inflammatory Mediators

Chapter 20: IL-1 Superfamily and Inflammasome
1. 20.1 Introduction
2. 20.2 IL-1α
3. 20.3 Cell Sources, Production, and Secretion
4. 20.4 IL-1β
5. 20.5 Systemic Effects of IL-1β in Humans
6. 20.6 IL-18 and IL-18-binding Protein
7. 20.7 IL-18 and Inflammation
8. 20.8 IL-18 as a Protective Cytokine
9. 20.9 IL-18-binding Protein
10. 20.10 IL-33
11. 20.11 IL-36
12. 20.12 IL-37
13. 20.13 Disease Models in IL37-tg Mice
14. 20.14 IL-38
15. References
Chapter 21: TNF Superfamily
1. 21.1 Introduction
2. 21.2 TNFα
3. 21.3 TNFα: Biological Roles
4. 21.4 Mechanisms of Action
5. 21.5 Characterization of the TNFα Gene and Molecule
6. 21.6 TNF Receptors and the TNF Receptor Superfamily
7. 21.7 TNF Family: Role on Inflammatory Bowel Diseases
8. 21.8 Role in Neuronal Inflammation
9. 21.9 Conclusions
10. References
Chapter 22: Interleukin-17 A-E
1. 22.1 Introduction
2. 22.2 Cell Sources of IL-17 Cytokines
3. 22.3 IL-17 Receptor: Structure and Biology
4. 22.4 Production and Role of IL-17 Cytokines in Normal and Inflamed Intestine
5. 22.5 IL-17 Blockers are Not Therapeutic in CD
6. 22.6 IL-17 Cytokines in Psoriasis
7. 22.7 Anti-IL-17 Therapy in Psoriasis
8. 22.8 IL-17A in Psoriatic Arthritis
9. 22.9 IL-17A in Rheumatoid Arthritis
10. 22.10 Clinical Findings
11. 22.11 IL-17B, IL-17C, and IL-17D
12. 22.12 IL-25 (IL-17E)
13. 22.13 Conclusions
14. References
Chapter 23: IL-6 Superfamily
1. 23.1 Introduction
2. 23.2 IL-6 and its Family of Cytokines
3. 23.3 Clinical Application of Members of IL-6 Family of Cytokines and Their Inhibitors
4. 23.4 Concluding Remarks
5. References
Chapter 24: Type I and II Cytokine Superfamilies in Inflammatory Responses
1. 24.1 Introduction
2. 24.2 Cytokine–Receptor Interactions
3. 24.3 Cytokine Superfamilies
4. 24.4 Summary: Cytokine Networks in Cellular Immunity
5. References
Chapter 25: Chemokines and Chemotaxis
1. 25.1 Introduction
2. 25.2 Chemokine and Chemokine Receptor Nomenclature Systems
3. 25.3 Extravasation of Leukocytes: The Multistep Model
4. 25.4 Inflammatory Chemokines and Homeostatic Chemokines
5. 25.5 The Structure of Chemokines
6. 25.6 Chemokine Receptors
7. 25.7 The Two-step Model of Chemokine Receptor Activation
8. 25.8 Signal Transduction
9. 25.9 Atypical Chemokine Receptors
10. 25.10 Organ Development and Chemokines
11. 25.11 The Primary Lymphoid Organs and Chemokines
12. 25.12 The Secondary Lymphoid Organs and Chemokines
13. 25.13 Memory/effector T Cells and Chemokine Receptors
14. 25.14 Mucosal Immunity and Chemokines
15. 25.15 Skin Immunity and Chemokines
16. 25.16 Clinical Applications
17. References
Chapter 26: Lipid Mediators in Inflammation
1. 26.1 Introduction: Biosynthesis, Degradation, and Receptors of Lipid Mediators
2. 26.2 PGs in Inflammation
3. 26.3 LTs in Inflammation
4. 26.4 Concluding Remarks
5. References
Chapter 27: Free Radicals in Inflammation
1. 27.1 Introduction
2. 27.2 What Are Free Radicals?
3. 27.3 Oxidative Stress and the Redox Code
4. 27.4 Free Radical Production: The Mitochondrion
5. 27.5 Reactive Oxygen Species
6. 27.6 Reactive Nitrogen Species
7. 27.7 Reactive Sulfur Species
8. 27.8 Making Redox Regulation Work: ROS, RNS, and RSS Acting in Concert at the Level of Thiols
9. 27.9 Antioxidants/Free Radical Scavengers
10. 27.10 The Redox Code in Health and Disease
11. 27.11 Looking to the Future: Newly Discovered Signaling Roles, the Reactive Species Interactome, and an Increasing Need to Assess the Role of Free Radicals in Personalized Medicine
12. 27.12 Conclusions: Free Radicals, the Reactive Species Interactome, and Its Importance to the Inflammatory Response
13. References
Chapter 28: Proteases
1. 28.1 Introduction
2. 28.2 Host Proteases and Inhibitors: Origin and Distribution
3. 28.3 Host Protease's Functions in Inflammation
4. 28.4 Microbial Proteases and Inflammation
5. 28.5 Proteases as Targets in Inflammatory Pathologies
6. 28.6 Conclusions
7. List of Abbreviations
8. Acknowledgments
9. References
Chapter 29: Psychiatric Disorders and Inflammation
1. 29.1 Introduction
2. 29.2 Association Studies between Inflammation and Psychiatric Disorders
3. 29.3 Mechanisms of the Association between Inflammation and Psychiatric Disorders
4. 29.4 Other Causal Factors for the Relationship between Inflammation and Psychiatric Disorders
5. 29.5 Relations between Inflammation and Neuropathology
6. 29.6 Conclusions
7. Acknowledgments
8. References
Chapter 30: Complement System
1. 30.1 Introduction
2. 30.2 Pathways of Complement Activation
3. 30.3 Activation Products of Complement
4. 30.4 Receptors for Complement Activation Products
5. 30.5 Role of Complement in Innate and Adaptive Immunity
6. 30.6 Evidence for Intracellular Activation of Complement
7. 30.7 Roles of C5a, C5aRs, and C3aR in Inflammatory Disorders
8. 30.8 Role of Complement in Selected Human Diseases
9. 30.9 Strategies to Block Complement Activation and Complement Activation Products
10. 30.10 Conclusions for Role of C3aR and C5aR
11. Acknowledgments
12. References
Chapter 31: Heat Shock Proteins
1. 31.1 The Molecules (HSP Families)
2. 31.2 Biological Function of HSPs (Chaperones)
3. 31.3 The Immunology of HSPs
4. 31.4 HSPs Protect in Models of Inflammatory Disease
5. 31.5 HSP as Inflammatory Mediators
6. 31.6 HSP are DAMPERs of Inflammation
7. 31.7 The Clinical use of HSP in Chronic Inflammatory Diseases
8. References

Part Four: Inflammation and Host Response

Chapter 32: Inflammation and Coagulation
1. 32.1 Introduction
2. 32.2 Incidence of Inflammation-associated Coagulopathy
3. 32.3 Clinical Relevance of the Interaction between Inflammation and Coagulation
4. 32.4 Pathogenetic Pathways in the Coagulopathy of Sepsis
5. 32.5 Modulation of Inflammation by Coagulation in vivo
6. 32.6 Injured Endothelium and Microparticles
7. 32.7 Systemic versus Localized Responses
8. 32.8 Organ-specific Responses by Endothelial Cells
9. 32.9 Diagnostic Approach to the Inflammation-induced Coagulopathy
10. 32.10 Supportive Treatment of Coagulation Abnormalities during Severe Inflammation
11. References
Chapter 33: Fever: Mediators and Mechanisms
1. 33.1 Introduction
2. 33.2 Fever: Physiological and Neuroanatomical Considerations
3. 33.3 Putative Peripherally Generated Endogenous Pyrogens
4. 33.4 Transfer of Fever-generating Signals Across the Blood–Brain Barrier
5. 33.5 Centrally Acting Pyrogenic Mediators and Processing of Febrile Signals in the Brain
6. 33.6 Clinical Aspects of Fever
7. 33.7 Concluding Remarks
8. List of Abbreviations
9. References
Chapter 34: Pain
1. 34.1 Introduction
2. 34.2 Basic Concepts of Pain
3. 34.3 Clinical Concepts of Pain
4. 34.4 Conclusions and Outlook
5. Acknowledgments
6. References
Chapter 35: Inflammation, Hormones, and Metabolism
1. 35.1 Introduction
2. 35.2 Thyroid Hormones
3. 35.3 Steroid Hormones
4. 35.4 Sex Hormones
5. 35.5 Pituitary Hormones
6. 35.6 Growth Hormone
7. 35.7 Adipokines
8. 35.8 Melanocortins
9. 35.9 Neuropeptide Y
10. 35.10 Orexin
11. 35.11 Bioenergetics + Metabolism
12. References
Chapter 36: Microenvironmental Regulation of Innate Immune Cell Function
1. 36.1 Introduction
2. 36.2 The role of Hypoxia in Regulating Innate Immune Cell Function
3. 36.3 Metabolism and Nutrient Availability
4. 36.4 Impact of Host–Pathogen Interactions on Innate Immune Cell Function
5. 36.5 Inflammatory Mediators
6. 36.6 Conclusions
7. References
Chapter 37: Epigenetics of Inflammation
1. 37.1 Epigenetics and Homeostasis Protection
2. 37.2 Epigenetic Principles
3. 37.3 Epigenetics of Successful Inflammation
4. 37.4 Epigenetics of Unsuccessful Inflammation
5. 37.5 Epigenetics and Immunometabolism
6. 37.6 Sirtuins: An Epigenetic Homeostat
7. 37.7 Epigenetic-based Inflammation Treatment
8. 37.8 Summary
9. References

Part Five: Inflammation and Diseases

Chapter 38: Allergy and Inflammation
1. 38.1 Introduction
2. 38.2 Innate Immunity and Its Role in Allergic Inflammation
3. 38.3 Adaptive Immunity and its Role in Allergic Inflammation
4. 38.4 Cytokines of Allergic Inflammation
5. References
Chapter 39: Sepsis
1. 39.1 Introduction
2. 39.2 Epidemiology
3. 39.3 Sepsis: Biology
4. 39.4 Clinical Management
5. 39.5 Definitions
6. 39.6 Conclusions
7. References
Chapter 40: Autoimmunity and Inflammation
1. 40.1 Introduction
2. 40.2 Immune Tolerance
3. 40.3 Genetic Factors that Break Immune Tolerance
4. 40.4 Environmental Factors that Break Immune Tolerance
5. 40.5 Autoimmune Tissue Injury: Tissue Inflammation
6. 40.6 Lupus Nephritis, a Paradigmatic Example of Systemic Autoimmunity and Autoimmune Tissue Injury
7. 40.7 Pathomechanisms of Systemic Lupus Erythematosus
8. 40.8 Pathomechanisms of Lupus Nephritis Operating Inside the Kidney
9. 40.9 Summary
10. Acknowledgments
11. Conflict of Interest Statement
12. References
Chapter 41: Psoriasis and Other Skin Inflammatory Diseases
1. 41.1 Introduction
2. 41.2 Normal Skin
3. 41.3 Psoriasis
4. 41.4 Other Inflammatory Skin Diseases
5. 41.5 Summary
6. Disclosures
7. Acknowledgments
8. References
Chapter 42: Rheumatoid Arthritis and Other Inflammatory Articular Diseases
1. 42.1 Inflammatory Articular Diseases
2. 42.2 Rheumatoid Arthritis
3. 42.3 Spondyloarthritides
4. 42.4 Conclusions
5. References
Chapter 43: Missing Heritability of Crohn's Disease and Implications for Therapeutic Targeting and Improved Care
1. 43.1 Crohn's Disease: A Public Health Issue
2. 43.2 An Imperative Need for Understanding Missing Heritability in Crohn's Disease
3. 43.3 Immunodeficiencies in Phagocytes as a Specific Cause of Crohn's Disease
4. 43.4 Concluding Remarks
5. References
Chapter 44: Inflammation and Transplantation
1. 44.1 Introduction
2. 44.2 Inflammation Increases the Expression of Transplant Antigens
3. 44.3 Inflammation Increases the Presentation of Transplant Antigens
4. 44.4 Inflammation Increases Antigen-Independent Activation Mediators
5. 44.5 Immediate Adaptive Immune Responses to Allografts
6. 44.6 De Novo Adaptive Responses to Transplants
7. 44.7 Acute Rejection Caused by T Lymphocytes
8. 44.8 Antibody-Mediated Acute Rejection
9. 44.9 Chronic Rejection
10. 44.10 Tolerance
11. 44.11 Tolerance and Accommodation of Blood Group Mismatched Transplants
12. 44.12 Organ-Specific Inflammation
13. 44.13 Treatment
14. 44.14 Modulating Inflammation to Improve Transplantation in the Future
15. Acknowledgment
16. References
Chapter 45: Inflammatory Mechanisms in Chronic Obstructive Pulmonary Disease
1. 45.1 Introduction
2. 45.2 Pathology of COPD
3. 45.3 Characteristics of COPD Inflammation
4. 45.4 Inflammatory Cells
5. 45.5 Inflammatory Mediators
6. 45.6 Oxidative Stress as a Major Driving Mechanism
7. 45.7 Systemic Inflammation in COPD
8. 45.8 Defective Resolution of Inflammation and Repair
9. 45.9 Future Implications
10. References
Chapter 46: Obesity: A Complex Disease with Immune Components
1. 46.1 Introduction
2. 46.2 Systemic inflammation: Circulating Cells as Contributors
3. 46.3 Macrophages in Obese Adipose Tissue
4. 46.4 T, Treg, B, NK, and Mast Cells
5. 46.5 Many Other Inflammatory Cell Effectors
6. 46.6 Impact of Adipose Inflammation on Local Biology: Numerous Molecular Effectors
7. 46.7 Adipose Inflammation and Obesity Complications
8. 46.8 Obesity as a Profibrotic Disease?
9. 46.9 Toward New Obesity Phenotypes and New Therapeutics?
10. 46.10 If a Certain Degree of Inflammation Is Beneficial, Is It Really Relevant to Consider a Therapeutic Modulation of Low-Grade Inflammation in Humans?
11. Acknowledgments
12. References
Chapter 47: Inflammation and Type 2 Diabetes
1. 47.1 Introduction
2. 47.2 Diabetes – Background and Epidemiology
3. 47.3 Obesity, Fat Distribution, and Inflammation
4. 47.4 How Does Inflammation Cause Type 2 Diabetes?
5. 47.5 How Does Inflammation Cause Vascular Disease in Type 2 Diabetes?
6. 47.6 Master Regulators and Potential Novel Targets to Counteract Obesity-Associated Inflammation in Type 2 Diabetes
7. 47.7 Concluding Remarks
8. References
Chapter 48: Inflammation-Mediated Neurodegeneration: Models, Mechanisms, and Therapeutic Interventions for Neurodegenerative Diseases
1. 48.1 Introduction
2. 48.2 Neuroinflammation Is a Double-Edged Sword in Neurodegenerative Diseases
3. 48.3 Inflammation-Related Models of Neurodegenerative Diseases
4. 48.4 Inflammatory Mechanisms of the Progressive Neurodegeneration
5. 48.5 Modulation of Neuroinflammation May Become a Disease-Modifying Therapy for Neurodegenerative Diseases
6. 48.6 Conclusions
7. Acknowledgments
8. Conflict of Interest
9. References
Chapter 49: Inflammation in Atherosclerosis
1. 49.1 Introduction
2. 49.2 Cholesterol Transport and Metabolism in Atherosclerosis
3. 49.3 Mouse Models of Atherosclerosis
4. 49.4 Triggers and Receptors of Inflammation in Atherosclerosis
5. 49.5 Mediators of Inflammation in Atherosclerosis
6. 49.6 Targeting Inflammation Atherosclerosis
7. 49.7 Conclusion
8. References
Chapter 50: Acute Kidney Injury
1. 50.1 Introduction
2. 50.2 Normal Kidney Anatomy and Physiology
3. 50.3 The Renal Response to Systemic Inflammation
4. 50.4 Summary
5. References
Chapter 51: Ischemia–Reperfusion Syndrome
1. 51.1 Introduction
2. 51.2 Pathophysiology
3. 51.3 Clinical Diseases
4. 51.4 Therapeutic Perspectives
5. 51.5 Conclusion
6. References
Chapter 52: Single-Nucleotide Polymorphisms and Inflammation
1. 52.1 The Principle
2. 52.2 SNPs and Functional Genomics
3. 52.3 Genetic Susceptibility for Acute Inflammatory Conditions
4. 52.4 Genetic Predisposition for Chronic Inflammatory Disorders
5. 52.5 Conclusive Remarks
6. References

Part Six: Resolution of Inflammation and Tissue Repair

Chapter 53: Pentraxins in the Orchestration of Defense and Tissue Repair during the Acute Phase Response
1. 53.1 The General Scenario
2. 53.2 Genes and Proteins
3. 53.3 Microbial Recognition
4. 53.4 Complement and FcγR
5. 53.5 Tissue Repair
6. 53.6 Concluding Remarks
7. References
Chapter 54: Anti-Inflammatory Cytokines, Soluble Receptors, and Natural Antagonists
1. 54.1 Introduction
2. 54.2 Anti-Inflammatory Cytokines and Soluble Receptors
3. 54.3 Negative Regulation of Toll-Like Receptor-Mediated Immune Responses
4. 54.4 Additional Anti-Inflammatory Mechanisms
5. 54.5 Concluding Remarks
6. References
Chapter 55: Regulatory T Cells
1. 55.1 Introduction
2. 55.2 TREG Subpopulations
3. 55.3 Control of Immunity to Self-Tissues by Foxp3+ TREGS
4. 55.4 TREGS in the Context of Infections
5. 55.5 Clinical Perspectives
6. Acknowledgments
7. References
Chapter 56: Leukocyte Reprogramming
1. 56.1 Introduction
2. 56.2 Endotoxin Tolerance
3. 56.3 Cross-tolerance
4. 56.4 From Endotoxin Tolerance to PRRs Ligands Tolerance
5. 56.5 Does Endotoxin Tolerance Affect Anti-Infectious Immunity?
6. 56.6 Clinical Relevance
7. 56.7 From Tolerance to Reprogramming
8. 56.8 Reversal
9. 56.9 Mechanisms
10. 56.10 Macrophage Plasticity
11. References
Chapter 57: Roles of Specialized Proresolving Lipid Mediators in Inflammation Resolution and Tissue Repair
1. 57.1 Resolution of Acute Inflammation: Identification of Specialized Proresolving Mediators
2. 57.2 Lipid Mediator Class Switching During Inflammation and Its Resolution
3. 57.3 Lipoxins
4. 57.4 E-series Resolvins
5. 57.5 D-series Resolvins
6. 57.6 Novel Statin-Induced 13-Series Resolvins
7. 57.7 Role of Novel Sulfido Lipid Mediator Conjugates in Tissue Regeneration
8. 57.8 Summary
9. Acknowledgments
10. References
Chapter 58: Glucocorticoids
1. 58.1 Introduction
2. 58.2 Pharmacokinetics
3. 58.3 Mechanisms of Action (Figure 58.2)
4. 58.4 Pharmacological Effects
5. 58.5 Therapeutic Use of Glucocorticoids
6. References
Chapter 59: The Neuroimmune Communicatome in Inflammation
1. 59.1 Introduction
2. 59.2 What is Inflammation?
3. 59.3 Neuroimmune Dialogue in Inflammation and the Concept of the Neuroimmune Communicatome
4. 59.4 Points of Interaction in the Neuroimmune Communicatome
5. 59.5 Translational Exploration Based on the Neuroimmune Communicatome
6. 59.6 Conclusions
7. Acknowledgments
8. Abbreviations
9. References
Chapter 60: The Inflammatory Response in Tissue Repair
1. 60.1 Introduction
2. 60.2 Initiation of the Inflammatory Response Following Injury: The Alarmins
3. 60.3 The Complement Cascade
4. 60.4 Induction and Release of Proinflammatory Cytokines
5. 60.5 Chemokines Regulate Leukocyte Recruitment
6. 60.6 Leukocyte Recruitment in Sites of Injury
7. 60.7 The Role of Neutrophils in Injured Tissues
8. 60.8 Repression and Resolution of Inflammation: The Stop Signals
9. 60.9 The Cellular Effectors of Resolution of Inflammation
10. 60.10 The Extracellular Matrix
11. 60.11 Tissue-Specific Events Leading to Regeneration
12. 60.12 Fibroblast Activation and Formation of a Scar
13. 60.13 Concluding Remarks
14. Sources of Funding
15. References

Part Seven: Detection and Treatments

Chapter 61: Biomarkers in Inflammation
1. 61.1 Acute-Phase Reactants
2. 61.2 Pentraxins
3. 61.3 C-Reactive Protein (CRP)
4. 61.4 Pentraxin 3
5. 61.5 Procalcitonin
6. 61.6 Interleukin 6
7. 61.7 Lipopolysaccharide-Binding Protein (LBP)
8. 61.8 Presepsin (Soluble CD14 Subtype)
9. 61.9 Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1)
10. 61.10 Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR)
11. 61.11 Adrenomedullin
12. 61.12 CD64
13. 61.13 Panels of Combined of Biomarkers
14. 61.14 Multiplexed Molecular Markers Derived from “Omics” Technologies
15. References
Chapter 62: In Vivo Imaging of Inflammation
1. 62.1 Introduction
2. 62.2 Methods for Inflammation Imaging
3. 62.3 Clinical Inflammation Imaging
4. 62.4 Emerging Protocols for Inflammation Imaging
5. References
Chapter 63: Novel Targets for Drug Development
1. 63.1 Introduction
2. 63.2 Conclusion
3. References
Chapter 64: Inflammation and Microbiota and Gut Reconditioning
1. 64.1 A Dramatic Increase in Incidence of Chronic Diseases
2. 64.2 The Epidemic Forecasted to Continue – Also in the Western World
3. 64.3 Developing Countries Soon to Take Over the “Yellow Jersey”
4. 64.4 Hypertension Associated with Dysbiosis
5. 64.5 Inflammation – A Mother of Disease
6. 64.6 The Gut Harbors the Majority of the Immune System
7. 64.7 Strong Association Between Composition of Microbiota and Chronic Diseases
8. 64.8 Paleolithic Forefathers Had a Much Different, Much More Diverse and Richer Microbiota
9. 64.9 Different Microbiota in Infants in Hunting and Gathering Communities
10. 64.10 The Most Robust Microbiota Ever Seen
11. 64.11 Rural Lifestyle Prevents Western Diseases
12. 64.12 Endotoxin (LPS) – A Major Inducer of Inflammation and Disease
13. 64.13 Meals Rich in Long-Chain Fatty Acids Induce Endotoxemia
14. 64.14 Humans Are Especially Sensitive to Endotoxin
15. 64.15 Fresh Fruits and Vegetables Contain Minimal Levels of Stimulants of Toll-Like Receptors (TLRs)
16. 64.16 Several Proteotoxins Stimulate Also Toll-Like Receptors (TLR) and Induce/Enhance Inflammation
17. 64.17 Gluten-Sensitivity a Common and Newly Detected Inflammation-Inducing Disorder
18. 64.18 Gluten-Free Foods Have Led to a New and Successful Industry
19. 64.19 Glutenoids Show Endotoxin-Mimicking Abilities
20. 64.20 Similar Effects Observed on Gluten Restriction in Individuals with ADHD
21. 64.21 Gluten Sensitivity Associated with Severe Dysbiosis, Leaky Gut and Increased General Inflammation
22. 64.22 Proteotoxin-Induced Low Threshold for Immune Response
23. 64.23 Heat- and Storage-Induced Inflammation-Inducing Proteins
24. 64.24 Numerous Proinflammatory Mediators Involved
25. 64.25 Short-Chain Fatty Acids – A Magic Bullet?
26. 64.26 Consumption of Plant Fibers Crucial to Eubiosis and Good Health
27. 64.27 Prebiotic Fibers Generally Resistant to Digestion in the Small Intestine
28. 64.28 It Is the Luminal Levels of SCFAs, Which Make the Difference
29. 64.29 Not only SCFAs but MCFAs Have Strong Ability to improve Immunity and Prevent Disease
30. 64.30 Stress Increases Microbial Growth and Virulence
31. 64.31 Early-Life Conditions Influence Long-Term Health
32. 64.32 Psychological Stress Impairs Microbiota
33. 64.33 Physical Exercise Increases Microbiota Numbers and Diversity
34. 64.34 Exercise Has Positive and Negative Effects on Immunity Depending on Its Intensity
35. 64.35 Postprandial Inflammation a “Deadly” Threat to Long-Term Health
36. 64.36 Abdominal/Visceral Obesity Enhances Postprandial Inflammation
37. 64.37 Postprandial Inflammation Are Induced by Long-Chain but Not Medium-Chain Fatty Acids
38. 64.38 Reduced Intake of LCFAs and Increased Intake of MCFAs Good for Microbiota and Health
39. 64.39 Gut Reconditioning – An Important Tool to Maintain Optimal Health
40. 64.40 Cancer
41. 64.41 Childhood Diarrhea
42. 64.42 Fecal Microbiota Transplantation (FMT) – A Giant Step Forward
43. 64.43 Synbiotics – A Less Invasive Alternative
44. 64.44 Less Suffering for the Patients – Great Savings for Society
45. 64.45 Ecobiological Functions – Same but Different Response Compared to So-Called Biological Drugs
46. References
Chapter 65: Natural Products as Source of Anti-Inflammatory Drugs
1. 65.1 Introduction
2. 65.2 Cellular, Molecular, and Biochemical Pathways of Inflammation
3. 65.3 Natural Products from Diverse Sources Possess Anti-Inflammatory Activity
4. 65.4 Technological Advancements in the Production, Characterization, and Delivery of Natural Products
5. 65.5 Concluding Remarks
6. References

Index

End User License Agreement

List of Tables

Table 2.1

Table 2.2

Table 6.1

Table 6.2

Table 6.3

Table 15.1

Table 15.2

Table 17.1

Table 17.2

Table 17.3

Table 19.1

Table 20.1

Table 23.1

Table 23.2

Table 25.1

Table 25.2

Table 25.3

Table 26.1

Table 26.2

Table 27.1

Table 28.1

Table 28.2

Table 28.3

Table 31.1

Table 34.1

Table 37.1

Table 37.2

Table 37.3

Table 40.1

Table 40.2

Table 40.3

Table 40.4

Table 40.5

Table 41.1

Table 41.2

Table 44.1

Table 52.1

Table 52.2

Table 52.3

Table 52.4

Table 53.1

Table 53.2

Table 54.1

Table 54.2

Table 58.1

Table 62.1

Table 63.1

Table 63.2

Table 63.3

Table 63.4

Table 65.1

Table 65.2

List of Illustrations

Figure 2.1

Figure 2.2

Figure 2.3

Figure 2.4

Figure 2.5

Figure 3.1

Figure 3.2

Figure 5.1

Figure 5.2

Figure 6.1

Figure 6.2

Figure 6.3

Figure 8.1

Figure 8.2

Figure 8.3

Figure 8.4

Figure 8.5

Figure 9.1

Figure 9.2

Figure 11.1

Figure 13.1

Figure 13.2

Figure 13.3

Figure 14.1

Figure 14.2

Figure 14.3

Figure 14.4

Figure 15.1

Figure 15.2

Figure 16.1

Figure 16.2

Figure 16.3

Figure 16.4

Figure 17.1

Figure 17.2

Figure 19.1

Figure 20.1

Figure 21.1

Figure 21.2

Figure 23.1

Figure 23.2

Figure 24.1

Figure 24.2

Figure 24.3

Figure 24.4

Figure 24.5

Figure 24.6

Figure 24.7

Figure 25.1

Figure 25.2

Figure 25.3

Figure 25.4

Figure 26.1

Figure 26.2

Figure 26.3

Figure 26.4

Figure 26.5

Figure 26.6

Figure 27.1

Figure 27.2

Figure 27.3

Figure 28.1

Figure 28.2

Figure 28.3

Figure 28.4

Figure 28.5

Figure 28.6

Figure 30.1

Figure 30.2

Figure 30.3

Figure 30.4

Figure 30.5

Figure 31.1

Figure 31.2

Figure 32.1

Figure 33.1

Figure 33.2

Figure 33.3

Figure 33.4

Figure 34.1

Figure 34.2

Figure 36.1

Figure 36.2

Figure 36.3

Figure 36.4

Figure 36.5

Figure 37.1

Figure 37.2

Figure 37.3

Figure 37.4

Figure 37.5

Figure 37.6

Figure 37.7

Figure 38.1

Figure 38.2

Figure 38.3

Figure 38.4

Figure 40.1

Figure 40.2

Figure 40.3

Figure 40.4

Figure 41.1

Figure 41.2

Figure 42.1

Figure 44.1

Figure 44.2

Figure 45.1

Figure 45.2

Figure 45.3

Figure 45.4

Figure 45.5

Figure 45.6

Figure 45.7

Figure 46.1

Figure 46.2

Figure 47.1

Figure 47.2

Figure 49.1

Figure 50.1

Figure 50.2

Figure 50.3

Figure 52.1

Figure 53.1

Figure 54.1

Figure 55.1

Figure 56.1

Figure 57.1

Figure 57.2

Figure 57.3

Figure 57.4

Figure 58.1

Figure 58.2

Figure 59.1

Figure 60.1

Figure 60.2

Figure 60.3

Figure 61.1

Figure 61.2

Figure 62.1

Figure 62.2

Figure 62.3

Figure 62.4

Figure 62.5

Figure 62.6

Figure 64.1

Figure 64.2

Figure 64.3

Figure 64.4

Figure 65.1

Figure 65.2

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Preface

Inflammation is older than humanity itself. Indeed, the earliest signs of inflammatory processes can be found on the bones of dinosaurs. Inflammation has always been integral to humans as the key process that protects against sterile or infectious insults. By the end of the eighteenth century, John Hunter was among the first to define inflammation as a salutary function, a concept endorsed 100 years later by Elie Metchnikoff. To limit the side effects of inflammation, the use of herbal anti-inflammatory was introduced in China (2800 BC) and Egypt (1520 BC), well before Hippocrates. Bloodletting was another therapeutic approach widely supported for some 2000 years. While natural products remain an important source of new anti-inflammatory drugs, bloodletting has been recognized to be powerless!

Nowadays, the beneficial effects of inflammation are well recognized when associated with the overlapping innate immune response. In recent years, molecular and cellular players have been well characterized and their precise interactions better understood. New molecular mechanisms have been deciphered such as the inflammasome and epigenetics. However, the word inflammation remains mainly associated with disease. Indeed, many chronic inflammatory disorders have been identified as severe debilitating diseases that may even favor the emergence of certain cancers. Deciphering the molecular and cellular events underlying inflammation has enabled development of new drugs that have revolutionized treatment and outcomes of some of these disorders.

Major achievements have been made in the last few decades allowing new understanding of the cross-talk between immune and nonimmune cells (e.g., cytokines, neuromediators, and eicosanoids) and in the resolution of inflammation (e.g., control by the neuronal system, new lipid mediators). Well-recognized leaders in the field have contributed their specific expertise to this book, thus making it most comprehensive overview of inflammatory processes and associated diseases.

Institut PasteurJean-Marc Cavaillon

Paris

France

University College LondonMervyn Singer

London, UK

From Molecular and Cellular Mechanisms to the Clinic