Inflammation E-Book

• Herausgeber: Wiley-VCH Verlag GmbH & Co. KGaA
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 3731

Veröffentlichungsjahr: 2017

Beschreibung

The leading reference on this topic of increasing medical relevance is unique in offering unparalleled coverage.
The editors are among the most respected researchers in inflammation worldwide and here have put together a prestigious team of contributors. Starting with the molecular basis of inflammation, from cytokines via the innate immune system to the different kinds of inflammatory cells, they continue with the function of inflammation in infectious disease before devoting a large section to the relationship between inflammation and chronic diseases. The book concludes with wound and tissue healing and options for therapeutic interventions.
A must have for clinicians and biomedical researchers alike.

Leseprobe

CONTENTS

Cover

Title Page

Copyright

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

2.1 Definition

2.2 Endotoxin

2.3 Other Bacterial PAMPs

2.4 Viral PAMPs

2.5 Parasitic PAMPs

2.6 Fungal PAMPs

2.7 Synergy

References

Chapter 3: Damage-associated Molecular Patterns

3.1 Definition

3.2 Necrosis versus Apoptosis

3.3 Receptors of Danger Signals

3.4 Main DAMPs

References

Chapter 4: Bacterial Toxins

4.1. Introduction

4.2 Toxins Modulating the Activity of Inflammatory Caspases and Inflammasomes

4.3 Toxins Modulating the Intracellular cAMP Levels

4.4 Toxins Modulating MAPK Signaling

4.5 Toxins Affecting Host Cell Motility

4.6 Toxins Blocking Protein Synthesis or Protein Folding

4.7 Conclusions

References

Chapter 5: Venoms

5.1 Introduction

5.2 Inflammation Induced by Snake Venoms

5.3 Inflammation Induced by Scorpion Venoms

5.4 Inflammation Induced by Spider Venoms

5.5 Inflammation Induced by Venoms of Bees, Vespids, and Ants

5.6 Conclusions

References

Chapter 6: Hypoxia as an Inducer of Inflammation

6.1 Introduction

6.2 Oxygen Sensing

6.3 Mitochondrial Oxygen Sensing

6.4 The Role of Transcription Factors

6.5 The Warburg Effect

6.6 Acute versus Chronic Hypoxia

6.7 Inflammasome Activation

6.8 Summary and Conclusions

References

Chapter 7: Vaccine Adjuvants

7.1 Introduction

7.2 Adjuvants Approved for Human Use

7.3 Aluminum Compounds: The Gold Standard

7.4 AS04

7.5 Calcium Phosphate

7.6 Emulsions

7.7 Nano/microparticles Including Liposomes and Virosomes

7.8 Immune Stimulating Complexes

7.9 Cytokines

7.10 Adjuvants that Target Toll-like Receptors

7.11 Adjuvant Combinations

7.12 Future Directions

References

Chapter 8: Pattern Recognition Receptors

8.1 Introduction

8.2 Toll-like Receptors

8.3 C-type Lectin Receptors

8.4 Natural Killer Gene Complex-associated CLRs

8.5 RIG-1-like Receptors

8.6 NOD-like Receptors

8.7 DNA-sensing Molecules

8.8 Conclusions

Acknowledgments

References

Part Two: Inflammatory Cells

Chapter 9: Monocytes and Macrophages

9.1 Introduction

9.2 Origin and Differentiation

9.3 Activation and Polarization

9.4 Functions

9.5 Molecular Pathways and Mechanisms Regulating Response

9.6 Conclusions

Acknowledgment

References

Chapter 10: Neutrophils

10.1 Characteristics

10.2 Hematopoiesis

10.3 Adhesion and Migration

10.4 Phagocytosis and Degranulation

10.5 Cytokine Synthesis

10.6 Neutrophil Apoptosis

10.7 Neutrophils in Pathology

10.8 Conclusions

References

Chapter 11: Mast Cells: Master Drivers of Immune Responses against Pathogens

11.1 Introduction

11.2 Biology of Mast Cells

11.3 Role of Mast Cells in Immune Surveillance

11.4 Mast Cells in Innate Immunity

11.5 Mast Cells in Adaptive Immunity

11.6 Enhancement of Immunity by Boosting Mast Cell Activity

11.7 Potentially Detrimental Roles of Mast Cell Activation during Immune Responses

11.8 Concluding Remarks

Acknowledgments

References

Chapter 12: Dendritic Cells in Inflammatory Disease

12.1 What Defines a Dendritic Cell?

12.2 Dendritic Cell Subsets

12.3 Dendritic Cells and T-cell Polarization

12.4 Dendritic Cells in Allergic Inflammation

12.5 Inflammatory DCs' Role in Human Allergy

12.6 Dendritic Cells in Autoimmune Inflammatory Disease

12.7 Conclusions

References

Chapter 13: Roles for NK Cells and ILC1 in Inflammation and Infection

13.1 Introduction

13.2 Distinguishing Group 1 ILC and NK Cells

13.3 NK Cell and ILC1 Activating and Inhibitory Receptors

13.4 Evidence for Distinct Subsets of NK Cells and ILC1

13.5 Effector Functions of NK Cells and ILC1

13.6 NK Cells and Group 1 ILCs in Inflammation and Infection

13.7 NK Cell and ILC1 Memory

13.8 Concluding Remarks: NK and ILC1 as Partners in a Type 1 Network

References

Chapter 14: Group 2 and 3 Innate Lymphoid Cells: New Actors in Immunity and Inflammation

14.1 ILCs: A New Family of Innate Effector Cells

14.2 ILC2 and ILC3 Heterogeneity and Homeostasis

14.3 ILC2 in Acute and Chronic Inflammation

14.4 ILC3 in Acute and Chronic Inflammation

14.5 Therapeutically Harnessing ILC2 and ILC3

14.6 Concluding Remarks

References

Chapter 15: Th9 Cells: From the Bench to the Bedside and Back Again

15.1 The History of T Helper Cells

15.2 Introduction to Th9 Cells

15.3 Th9 Cells in Disease: The Helpful and Unhelpful

15.4 Targeting Th9 Cells Therapeutically

15.5 Summary and Future Directions

References

Chapter 16: Th17 Cells

16.1 Introduction

16.2 Differentiation of Th17 Cells

16.3 Cytokines and Chemokines Related to Th17 Cells

16.4 Th17 and Inflammatory Diseases

16.5 Mechanisms in Chronic Inflammation

16.6 Plasticity of Th17 Cells

16.7 Clinical Targeting of Th17 Cells

16.8 Conclusions

Acknowledgment

References

Chapter 17: Platelets

17.1 Introduction

17.2 Expression of Toll-like Receptors

17.3 Interactions between Platelets and Bacteria

17.4 Interactions between Platelets and White Blood Cells

17.5 Platelet Integrins

17.6 Role of Platelets in Immune Responses

17.7 Platelets and Inflammatory Disorders

17.8 Malaria

17.9 Systemic Lupus Erythematosus

17.10 Conclusions

References

Chapter 18: Epithelial Cells

18.1 Introduction

18.2 The Intestinal Epithelium: An Archetypal Epithelial Barrier

18.3 Choosing a Cell Fate: The Absorptive Lineage

18.4 Choosing a Cell Fate: The Secretory Lineage

18.5 The Epithelium: The Sum is Greater than its Parts

18.6 Epithelial Homeostasis: Maintaining the Balance

18.7 Concluding Remarks

References

Chapter 19: Inflammation: The Role of Endothelial Cells

19.1 Introduction

19.2 Vasomotor Dysfunction

19.3 Conclusions

References

Part Three: Inflammatory Mediators

Chapter 20: IL-1 Superfamily and Inflammasome

20.1 Introduction

20.2 IL-1α

20.3 Cell Sources, Production, and Secretion

20.4 IL-1β

20.5 Systemic Effects of IL-1β in Humans

20.6 IL-18 and IL-18-binding Protein

20.7 IL-18 and Inflammation

20.8 IL-18 as a Protective Cytokine

20.9 IL-18-binding Protein

20.10 IL-33

20.11 IL-36

20.12 IL-37

20.13 Disease Models in IL37-tg Mice

20.14 IL-38

References

Chapter 21: TNF Superfamily

21.1 Introduction

21.2 TNFα

21.3 TNFα: Biological Roles

21.4 Mechanisms of Action

21.5 Characterization of the TNFα Gene and Molecule

21.6 TNF Receptors and the TNF Receptor Superfamily

21.7 TNF Family: Role on Inflammatory Bowel Diseases

21.8 Role in Neuronal Inflammation

21.9 Conclusions

References

Chapter 22: Interleukin-17 A-E

22.1 Introduction

22.2 Cell Sources of IL-17 Cytokines

22.3 IL-17 Receptor: Structure and Biology

22.4 Production and Role of IL-17 Cytokines in Normal and Inflamed Intestine

22.5 IL-17 Blockers are Not Therapeutic in CD

22.6 IL-17 Cytokines in Psoriasis

22.7 Anti-IL-17 Therapy in Psoriasis

22.8 IL-17A in Psoriatic Arthritis

22.9 IL-17A in Rheumatoid Arthritis

22.10 Clinical Findings

22.11 IL-17B, IL-17C, and IL-17D

22.12 IL-25 (IL-17E)

22.13 Conclusions

References

Chapter 23: IL-6 Superfamily

23.1 Introduction

23.2 IL-6 and its Family of Cytokines

23.3 Clinical Application of Members of IL-6 Family of Cytokines and Their Inhibitors

23.4 Concluding Remarks

References

Chapter 24: Type I and II Cytokine Superfamilies in Inflammatory Responses

24.1 Introduction

24.2 Cytokine–Receptor Interactions

24.3 Cytokine Superfamilies

24.4 Summary: Cytokine Networks in Cellular Immunity

References

Chapter 25: Chemokines and Chemotaxis

25.1 Introduction

25.2 Chemokine and Chemokine Receptor Nomenclature Systems

25.3 Extravasation of Leukocytes: The Multistep Model

25.4 Inflammatory Chemokines and Homeostatic Chemokines

25.5 The Structure of Chemokines

25.6 Chemokine Receptors

25.7 The Two-step Model of Chemokine Receptor Activation

25.8 Signal Transduction

25.9 Atypical Chemokine Receptors

25.10 Organ Development and Chemokines

25.11 The Primary Lymphoid Organs and Chemokines

25.12 The Secondary Lymphoid Organs and Chemokines

25.13 Memory/effector T Cells and Chemokine Receptors

25.14 Mucosal Immunity and Chemokines

25.15 Skin Immunity and Chemokines

25.16 Clinical Applications

References

Chapter 26: Lipid Mediators in Inflammation

26.1 Introduction: Biosynthesis, Degradation, and Receptors of Lipid Mediators

26.2 PGs in Inflammation

26.3 LTs in Inflammation

26.4 Concluding Remarks

References

Chapter 27: Free Radicals in Inflammation

27.1 Introduction

27.2 What Are Free Radicals?

27.3 Oxidative Stress and the Redox Code

27.4 Free Radical Production: The Mitochondrion

27.5 Reactive Oxygen Species

27.6 Reactive Nitrogen Species

27.7 Reactive Sulfur Species

27.8 Making Redox Regulation Work: ROS, RNS, and RSS Acting in Concert at the Level of Thiols

27.9 Antioxidants/Free Radical Scavengers

27.10 The Redox Code in Health and Disease

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

27.12 Conclusions: Free Radicals, the Reactive Species Interactome, and Its Importance to the Inflammatory Response

References

Chapter 28: Proteases

28.1 Introduction

28.2 Host Proteases and Inhibitors: Origin and Distribution

28.3 Host Protease's Functions in Inflammation

28.4 Microbial Proteases and Inflammation

28.5 Proteases as Targets in Inflammatory Pathologies

28.6 Conclusions

List of Abbreviations

Acknowledgments

References

Chapter 29: Psychiatric Disorders and Inflammation

29.1 Introduction

29.2 Association Studies between Inflammation and Psychiatric Disorders

29.3 Mechanisms of the Association between Inflammation and Psychiatric Disorders

29.4 Other Causal Factors for the Relationship between Inflammation and Psychiatric Disorders

29.5 Relations between Inflammation and Neuropathology

29.6 Conclusions

Acknowledgments

References

Chapter 30: Complement System

30.1 Introduction

30.2 Pathways of Complement Activation

30.3 Activation Products of Complement

30.4 Receptors for Complement Activation Products

30.5 Role of Complement in Innate and Adaptive Immunity

30.6 Evidence for Intracellular Activation of Complement

30.7 Roles of C5a, C5aRs, and C3aR in Inflammatory Disorders

30.8 Role of Complement in Selected Human Diseases

30.9 Strategies to Block Complement Activation and Complement Activation Products

30.10 Conclusions for Role of C3aR and C5aR

Acknowledgments

References

Chapter 31: Heat Shock Proteins

31.1 The Molecules (HSP Families)

31.2 Biological Function of HSPs (Chaperones)

31.3 The Immunology of HSPs

31.4 HSPs Protect in Models of Inflammatory Disease

31.5 HSP as Inflammatory Mediators

31.6 HSP are DAMPERs of Inflammation

31.7 The Clinical use of HSP in Chronic Inflammatory Diseases

References

Part Four: Inflammation and Host Response

Chapter 32: Inflammation and Coagulation

32.1 Introduction

32.2 Incidence of Inflammation-associated Coagulopathy

32.3 Clinical Relevance of the Interaction between Inflammation and Coagulation

32.4 Pathogenetic Pathways in the Coagulopathy of Sepsis

32.5 Modulation of Inflammation by Coagulation in vivo

32.6 Injured Endothelium and Microparticles

32.7 Systemic versus Localized Responses

32.8 Organ-specific Responses by Endothelial Cells

32.9 Diagnostic Approach to the Inflammation-induced Coagulopathy

32.10 Supportive Treatment of Coagulation Abnormalities during Severe Inflammation

References

Chapter 33: Fever: Mediators and Mechanisms

33.1 Introduction

33.2 Fever: Physiological and Neuroanatomical Considerations

33.3 Putative Peripherally Generated Endogenous Pyrogens

33.4 Transfer of Fever-generating Signals Across the Blood–Brain Barrier

33.5 Centrally Acting Pyrogenic Mediators and Processing of Febrile Signals in the Brain

33.6 Clinical Aspects of Fever

33.7 Concluding Remarks

List of Abbreviations

References

Chapter 34: Pain

34.1 Introduction

34.2 Basic Concepts of Pain

34.3 Clinical Concepts of Pain

34.4 Conclusions and Outlook

Acknowledgments

References

Chapter 35: Inflammation, Hormones, and Metabolism

35.1 Introduction

35.2 Thyroid Hormones

35.3 Steroid Hormones

35.4 Sex Hormones

35.5 Pituitary Hormones

35.6 Growth Hormone

35.7 Adipokines

35.8 Melanocortins

35.9 Neuropeptide Y

35.10 Orexin

35.11 Bioenergetics + Metabolism

References

Chapter 36: Microenvironmental Regulation of Innate Immune Cell Function

36.1 Introduction

36.2 The role of Hypoxia in Regulating Innate Immune Cell Function

36.3 Metabolism and Nutrient Availability

36.4 Impact of Host–Pathogen Interactions on Innate Immune Cell Function

36.5 Inflammatory Mediators

36.6 Conclusions

References

Chapter 37: Epigenetics of Inflammation

37.1 Epigenetics and Homeostasis Protection

37.2 Epigenetic Principles

37.3 Epigenetics of Successful Inflammation

37.4 Epigenetics of Unsuccessful Inflammation

37.5 Epigenetics and Immunometabolism

37.6 Sirtuins: An Epigenetic Homeostat

37.7 Epigenetic-based Inflammation Treatment

37.8 Summary

References

Part Five: Inflammation and Diseases

Chapter 38: Allergy and Inflammation

38.1 Introduction

38.2 Innate Immunity and Its Role in Allergic Inflammation

38.3 Adaptive Immunity and its Role in Allergic Inflammation

38.4 Cytokines of Allergic Inflammation

References

Chapter 39: Sepsis

39.1 Introduction

39.2 Epidemiology

39.3 Sepsis: Biology

39.4 Clinical Management

39.5 Definitions

39.6 Conclusions

References

Chapter 40: Autoimmunity and Inflammation

40.1 Introduction

40.2 Immune Tolerance

40.3 Genetic Factors that Break Immune Tolerance

40.4 Environmental Factors that Break Immune Tolerance

40.5 Autoimmune Tissue Injury: Tissue Inflammation

40.6 Lupus Nephritis, a Paradigmatic Example of Systemic Autoimmunity and Autoimmune Tissue Injury

40.7 Pathomechanisms of Systemic Lupus Erythematosus

40.8 Pathomechanisms of Lupus Nephritis Operating Inside the Kidney

40.9 Summary

Acknowledgments

Conflict of Interest Statement

References

Chapter 41: Psoriasis and Other Skin Inflammatory Diseases

41.1 Introduction

41.2 Normal Skin

41.3 Psoriasis

41.4 Other Inflammatory Skin Diseases

41.5 Summary

Disclosures

Acknowledgments

References

Chapter 42: Rheumatoid Arthritis and Other Inflammatory Articular Diseases

42.1 Inflammatory Articular Diseases

42.2 Rheumatoid Arthritis

42.3 Spondyloarthritides

42.4 Conclusions

References

Chapter 43: Missing Heritability of Crohn's Disease and Implications for Therapeutic Targeting and Improved Care

43.1 Crohn's Disease: A Public Health Issue

43.2 An Imperative Need for Understanding Missing Heritability in Crohn's Disease

43.3 Immunodeficiencies in Phagocytes as a Specific Cause of Crohn's Disease

43.4 Concluding Remarks

References

Chapter 44: Inflammation and Transplantation

44.1 Introduction

44.2 Inflammation Increases the Expression of Transplant Antigens

44.3 Inflammation Increases the Presentation of Transplant Antigens

44.4 Inflammation Increases Antigen-Independent Activation Mediators

44.5 Immediate Adaptive Immune Responses to Allografts

44.6 De Novo Adaptive Responses to Transplants

44.7 Acute Rejection Caused by T Lymphocytes

44.8 Antibody-Mediated Acute Rejection

44.9 Chronic Rejection

44.10 Tolerance

44.11 Tolerance and Accommodation of Blood Group Mismatched Transplants

44.12 Organ-Specific Inflammation

44.13 Treatment

44.14 Modulating Inflammation to Improve Transplantation in the Future

Acknowledgment

References

Chapter 45: Inflammatory Mechanisms in Chronic Obstructive Pulmonary Disease

45.1 Introduction

45.2 Pathology of COPD

45.3 Characteristics of COPD Inflammation

45.4 Inflammatory Cells

45.5 Inflammatory Mediators

45.6 Oxidative Stress as a Major Driving Mechanism

45.7 Systemic Inflammation in COPD

45.8 Defective Resolution of Inflammation and Repair

45.9 Future Implications

References

Chapter 46: Obesity: A Complex Disease with Immune Components

46.1 Introduction

46.2 Systemic inflammation: Circulating Cells as Contributors

46.3 Macrophages in Obese Adipose Tissue

46.4 T, Treg, B, NK, and Mast Cells

46.5 Many Other Inflammatory Cell Effectors

46.6 Impact of Adipose Inflammation on Local Biology: Numerous Molecular Effectors

46.7 Adipose Inflammation and Obesity Complications

46.8 Obesity as a Profibrotic Disease?

46.9 Toward New Obesity Phenotypes and New Therapeutics?

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?

Acknowledgments

References

Chapter 47: Inflammation and Type 2 Diabetes

47.1 Introduction

47.2 Diabetes – Background and Epidemiology

47.3 Obesity, Fat Distribution, and Inflammation

47.4 How Does Inflammation Cause Type 2 Diabetes?

47.5 How Does Inflammation Cause Vascular Disease in Type 2 Diabetes?

47.6 Master Regulators and Potential Novel Targets to Counteract Obesity-Associated Inflammation in Type 2 Diabetes

47.7 Concluding Remarks

References

Chapter 48: Inflammation-Mediated Neurodegeneration: Models, Mechanisms, and Therapeutic Interventions for Neurodegenerative Diseases

48.1 Introduction

48.2 Neuroinflammation Is a Double-Edged Sword in Neurodegenerative Diseases

48.3 Inflammation-Related Models of Neurodegenerative Diseases

48.4 Inflammatory Mechanisms of the Progressive Neurodegeneration

48.5 Modulation of Neuroinflammation May Become a Disease-Modifying Therapy for Neurodegenerative Diseases

48.6 Conclusions

Acknowledgments

Conflict of Interest

References

Chapter 49: Inflammation in Atherosclerosis

49.1 Introduction

49.2 Cholesterol Transport and Metabolism in Atherosclerosis

49.3 Mouse Models of Atherosclerosis

49.4 Triggers and Receptors of Inflammation in Atherosclerosis

49.5 Mediators of Inflammation in Atherosclerosis

49.6 Targeting Inflammation Atherosclerosis

49.7 Conclusion

References

Chapter 50: Acute Kidney Injury

50.1 Introduction

50.2 Normal Kidney Anatomy and Physiology

50.3 The Renal Response to Systemic Inflammation

50.4 Summary

References

Chapter 51: Ischemia–Reperfusion Syndrome

51.1 Introduction

51.2 Pathophysiology

51.3 Clinical Diseases

51.4 Therapeutic Perspectives

51.5 Conclusion

References

Chapter 52: Single-Nucleotide Polymorphisms and Inflammation

52.1 The Principle

52.2 SNPs and Functional Genomics

52.3 Genetic Susceptibility for Acute Inflammatory Conditions

52.4 Genetic Predisposition for Chronic Inflammatory Disorders

52.5 Conclusive Remarks

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

53.1 The General Scenario

53.2 Genes and Proteins

53.3 Microbial Recognition

53.4 Complement and FcγR

53.5 Tissue Repair

53.6 Concluding Remarks

References

Chapter 54: Anti-Inflammatory Cytokines, Soluble Receptors, and Natural Antagonists

54.1 Introduction

54.2 Anti-Inflammatory Cytokines and Soluble Receptors

54.3 Negative Regulation of Toll-Like Receptor-Mediated Immune Responses

54.4 Additional Anti-Inflammatory Mechanisms

54.5 Concluding Remarks

References

Chapter 55: Regulatory T Cells

55.1 Introduction

55.2 TREG Subpopulations

55.3 Control of Immunity to Self-Tissues by Foxp3+ TREGS

55.4 TREGS in the Context of Infections

55.5 Clinical Perspectives

Acknowledgments

References

Chapter 56: Leukocyte Reprogramming

56.1 Introduction

56.2 Endotoxin Tolerance

56.3 Cross-tolerance

56.4 From Endotoxin Tolerance to PRRs Ligands Tolerance

56.5 Does Endotoxin Tolerance Affect Anti-Infectious Immunity?

56.6 Clinical Relevance

56.7 From Tolerance to Reprogramming

56.8 Reversal

56.9 Mechanisms

56.10 Macrophage Plasticity

References

Chapter 57: Roles of Specialized Proresolving Lipid Mediators in Inflammation Resolution and Tissue Repair

57.1 Resolution of Acute Inflammation: Identification of Specialized Proresolving Mediators

57.2 Lipid Mediator Class Switching During Inflammation and Its Resolution

57.3 Lipoxins

57.4 E-series Resolvins

57.5 D-series Resolvins

57.6 Novel Statin-Induced 13-Series Resolvins

57.7 Role of Novel Sulfido Lipid Mediator Conjugates in Tissue Regeneration

57.8 Summary

Acknowledgments

References

Chapter 58: Glucocorticoids

58.1 Introduction

58.2 Pharmacokinetics

58.3 Mechanisms of Action (Figure 58.2)

58.4 Pharmacological Effects

58.5 Therapeutic Use of Glucocorticoids

References

Chapter 59: The Neuroimmune Communicatome in Inflammation

59.1 Introduction

59.2 What is Inflammation?

59.3 Neuroimmune Dialogue in Inflammation and the Concept of the Neuroimmune Communicatome

59.4 Points of Interaction in the Neuroimmune Communicatome

59.5 Translational Exploration Based on the Neuroimmune Communicatome

59.6 Conclusions

Acknowledgments

Abbreviations

References

Chapter 60: The Inflammatory Response in Tissue Repair

60.1 Introduction

60.2 Initiation of the Inflammatory Response Following Injury: The Alarmins

60.3 The Complement Cascade

60.4 Induction and Release of Proinflammatory Cytokines

60.5 Chemokines Regulate Leukocyte Recruitment

60.6 Leukocyte Recruitment in Sites of Injury

60.7 The Role of Neutrophils in Injured Tissues

60.8 Repression and Resolution of Inflammation: The Stop Signals

60.9 The Cellular Effectors of Resolution of Inflammation

60.10 The Extracellular Matrix

60.11 Tissue-Specific Events Leading to Regeneration

60.12 Fibroblast Activation and Formation of a Scar

60.13 Concluding Remarks

Sources of Funding

References

Part Seven: Detection and Treatments

Chapter 61: Biomarkers in Inflammation

61.1 Acute-Phase Reactants

61.2 Pentraxins

61.3 C-Reactive Protein (CRP)

61.4 Pentraxin 3

61.5 Procalcitonin

61.6 Interleukin 6

61.7 Lipopolysaccharide-Binding Protein (LBP)

61.8 Presepsin (Soluble CD14 Subtype)

61.9 Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1)

61.10 Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR)

61.11 Adrenomedullin

61.12 CD64

61.13 Panels of Combined of Biomarkers

61.14 Multiplexed Molecular Markers Derived from “Omics” Technologies

References

Chapter 62: In Vivo Imaging of Inflammation

62.1 Introduction

62.2 Methods for Inflammation Imaging

62.3 Clinical Inflammation Imaging

62.4 Emerging Protocols for Inflammation Imaging

References

Chapter 63: Novel Targets for Drug Development

63.1 Introduction

63.2 Conclusion

References

Chapter 64: Inflammation and Microbiota and Gut Reconditioning

64.1 A Dramatic Increase in Incidence of Chronic Diseases

64.2 The Epidemic Forecasted to Continue – Also in the Western World

64.3 Developing Countries Soon to Take Over the “Yellow Jersey”

64.4 Hypertension Associated with Dysbiosis

64.5 Inflammation – A Mother of Disease

64.6 The Gut Harbors the Majority of the Immune System

64.7 Strong Association Between Composition of Microbiota and Chronic Diseases

64.8 Paleolithic Forefathers Had a Much Different, Much More Diverse and Richer Microbiota

64.9 Different Microbiota in Infants in Hunting and Gathering Communities

64.10 The Most Robust Microbiota Ever Seen

64.11 Rural Lifestyle Prevents Western Diseases

64.12 Endotoxin (LPS) – A Major Inducer of Inflammation and Disease

64.13 Meals Rich in Long-Chain Fatty Acids Induce Endotoxemia

64.14 Humans Are Especially Sensitive to Endotoxin

64.15 Fresh Fruits and Vegetables Contain Minimal Levels of Stimulants of Toll-Like Receptors (TLRs)

64.16 Several Proteotoxins Stimulate Also Toll-Like Receptors (TLR) and Induce/Enhance Inflammation

64.17 Gluten-Sensitivity a Common and Newly Detected Inflammation-Inducing Disorder

64.18 Gluten-Free Foods Have Led to a New and Successful Industry

64.19 Glutenoids Show Endotoxin-Mimicking Abilities

64.20 Similar Effects Observed on Gluten Restriction in Individuals with ADHD

64.21 Gluten Sensitivity Associated with Severe Dysbiosis, Leaky Gut and Increased General Inflammation

64.22 Proteotoxin-Induced Low Threshold for Immune Response

64.23 Heat- and Storage-Induced Inflammation-Inducing Proteins

64.24 Numerous Proinflammatory Mediators Involved

64.25 Short-Chain Fatty Acids – A Magic Bullet?

64.26 Consumption of Plant Fibers Crucial to Eubiosis and Good Health

64.27 Prebiotic Fibers Generally Resistant to Digestion in the Small Intestine

64.28 It Is the Luminal Levels of SCFAs, Which Make the Difference

64.29 Not only SCFAs but MCFAs Have Strong Ability to improve Immunity and Prevent Disease

64.30 Stress Increases Microbial Growth and Virulence

64.31 Early-Life Conditions Influence Long-Term Health

64.32 Psychological Stress Impairs Microbiota

64.33 Physical Exercise Increases Microbiota Numbers and Diversity

64.34 Exercise Has Positive and Negative Effects on Immunity Depending on Its Intensity

64.35 Postprandial Inflammation a “Deadly” Threat to Long-Term Health

64.36 Abdominal/Visceral Obesity Enhances Postprandial Inflammation

64.37 Postprandial Inflammation Are Induced by Long-Chain but Not Medium-Chain Fatty Acids

64.38 Reduced Intake of LCFAs and Increased Intake of MCFAs Good for Microbiota and Health

64.39 Gut Reconditioning – An Important Tool to Maintain Optimal Health

64.40 Cancer

64.41 Childhood Diarrhea

64.42 Fecal Microbiota Transplantation (FMT) – A Giant Step Forward

64.43 Synbiotics – A Less Invasive Alternative

64.44 Less Suffering for the Patients – Great Savings for Society

64.45 Ecobiological Functions – Same but Different Response Compared to So-Called Biological Drugs

References

Chapter 65: Natural Products as Source of Anti-Inflammatory Drugs

65.1 Introduction

65.2 Cellular, Molecular, and Biochemical Pathways of Inflammation

65.3 Natural Products from Diverse Sources Possess Anti-Inflammatory Activity

65.4 Technological Advancements in the Production, Characterization, and Delivery of Natural Products

65.5 Concluding Remarks

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

Guide

Cover

Table of Contents

Preface

Part 1

Chapter 1

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Inflammation

From Molecular and Cellular Mechanisms to the Clinic

Volume 1,2,3 and 4

Edited by Jean-Marc Cavaillon and Mervyn Singer

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

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© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978-3-527-33899-3

ePDF ISBN: 978-3-527-69218-7

ePub ISBN: 978-3-527-69216-3

Mobi ISBN: 978-3-527-69217-0

oBook ISBN: 978-3-527-69215-6

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

1Inflammation through the Ages: A Historical Perspective

Jean-Marc Cavaillon

Institut Pasteur, Unit Cytokines & Inflammation, 28 rue Dr. Roux, 75015 Paris, France

1.1 Introduction

Inflammation is older than humanity itself and the earliest signs of inflammatory processes can be found on the bones of dinosaurs. Of course, inflammation has always been accompanying humans since they are on Earth as it can be seen on the bones of the first humanoids and of Homo sapiens. The first precise diagnoses of inflammatory disorders were made on Egyptian mummies by Sir Marc Armand Ruffer (1859–1917). Accompanying the first British Egyptologists, he gave birth to a new science: “paleopathology.” He made a pioneer post-mortem diagnosis of arthritis and spondylitis, and by studying the mummy of Ramses II, he diagnosed that the pharaoh had suffered from atherosclerosis. In fact, long before inflammatory processes could be understood or even defined humans had proposed various therapeutic approaches to treat different types of inflammatory diseases.

1.2 The First Treatments

According to Chinese mythology, herbology or the use of plants to cure diseases was introduced by Emperor Shennong in 2800 BC, and the first ever book on medicinal plants was published in China in 300–200 BC. Other testimonies of interest on plants to cure diseases or at least to relieve pain and fever were provided by Edwin Smith and Georg Moritz Ebers, two Egyptologists who obtained fascinating papyruses. These papyruses (around 1520 BC) were copies of even older ones (3400 BC). Not only did they describe case reports of injuries but also listed different plants to be used against various types of injuries (crocodile bites, burns, fractures, bowel diseases, joint pains, etc). For example, infusion of dried myrtle was recommended for rheumatic pain. The interest to use plants to cure inflammatory diseases was perpetuated by the Greeks, and Hippocrates (450–370 BC) used extracts from willow bark to relieve pain and fever. The study of willow bark ended with the discovery of aspirin in the nineteenth century.

Hippocrates also advocated bloodletting as another therapeutic approach to cure most diseases, including inflammatory disorders. Its use was supported by other erudite Greeks such as Erasistratus, Asclepiades of Bithynia, or Galen of Pergamon and later by the Roman scholar Aulus Cornelius Celsus, the Persian medical doctor Avicenna (tenth century), or the Spanish Jewish doctor Moïse Maïmonide (twelfth century). All physicians of the kings of France were great supporters of bloodletting. Ambroise Paré (1509–1590), the physician of Charles IX, explained why he bled a young man 27 times in four days: “I liked to mention this event, so that the young surgeon will not be too shy to draw blood when confronted to large inflammation.” Laurent Joubert (1529–1583), the physician of Henri III, claimed that it was a way to get rid of the “bad blood” while the best was retained. Charles Bouvard (1572–1658) had probably prescribed 47 bloodlettings during the last 10 years of Louis XIII who died of Crohn's disease at the age of 42 years. They used it even when their patients were still young. For instance, François Vaultier (1590–1652) bled the young Louis XIV at the age of 9 years when he had smallpox. Guy Patin (1601–1672), the dean of the School of Medicine in Paris for a brief period, declared: “There is no remedy in the world that does so many miracles. I have bled my wife twelve times for a pleurisy, twenty times my son for a continuous fever and myself seven times for a cold.” [1] Even on the American continent, bloodletting was popular. Thus, on December 14, 1799, Georges Washington, probably suffering from pneumonia, died when 3.7 l of blood was drained out of his body in one single day. The first doctor to question the usefulness of bloodletting was Pierre Charles Alexandre Louis (1787–1872) who in 1835 considered this approach to have had very limited advantages. But pitted against him were leading doctors such as François Broussais (1772–1838) who was alleged to have had spilled more blood than Napoleon on all battlefields! If the lancet was commonly used to remove blood from patients, then the use of leeches was another method. According to an estimate, 35 million leeches were used in France in 1830 alone. This trend went unabated until François-Vincent Raspail (1794–1878) questioned the method in 1845 saying: “But why resort to violent and bloody means? Do you wish to calm fever? You will not succeed by bleeding […] So leave your lancet there, it has made enough troubles since Hippocrates” [2]. In 1856, in Great Britain, John Hughes Bennet (1812–1875) also concluded that there was no proven therapeutic advantage of bloodletting.

The other method used to prevent a severe inflammation and infection after a wound was cauterization supported by doctors such as Giovanni da Vigo (1450–1525) in Italy and Paracelsus (1493–1541) in Switzerland until Ambroise Paré, comparing the relative advantages of cauterization and the use of antiseptics, concluded that the latter were the best. But the word “antiseptic” was coined only in 1750 by John Pringle (1707–1782), a Scottish physician, who studied numerous substances able to prevent putrefaction. In 1854, Florence Nightingale (1820–1910) advocated hygiene as a means to prevent infection during the Crimean war in order to limit the mortality of wounded soldiers. Of course, the main advocate of hygiene was Ignaz Semmelweis (1818–1865) who succeeded in 1847 to reduce mortality due to puerperal sepsis.

1.3 The Definitions

One of the very firsts to define the parameters of inflammation was Aulus Cornelius Celsus (25 BC–50 AD), a Roman encyclopedist to whom we owe the famous statement: “Notae vero inflammationis sunt quatuor: rubor et tumor cum calore and dolore” (The signs of inflammation are four: redness, swelling, fever and pain). A fifth element was later added “loss of organ function.” Erroneously attributed to Galen of Pergamum, it could have been proposed by either Thomas Sydenham (1624–1689) or Rudolf Virchow (1821–1902). Of course, inflammation has for a long time been considered a morbid response of the host to any types of insults. However, John Hunter (1728–1793), a Scottish surgeon, appropriately defined inflammation in his book published one year after his death: “Inflammation in itself is not to be considered as a disease, but as a salutary operation, consequent either to some violence or some disease” [3]. Despite this appropriate definition, one could still read in 1865 in the French dictionary of medicine that “Inflammation is a complex morbid phenomenon, particularly associated with the function of blood circulation.” In his lecture on inflammation, Elie Metchnikoff (1845–1916) stated in 1891 that phagocytes were the participant of the inflammatory process and that inflammation should no longer be seen as only being deleterious [4]. Since Metchnikoff, many mechanisms accompanying inflammation have been further deciphered and mediators have been characterized.

1.4 Fever

For a while it was believed that fever was consecutive to some obstructions within the blood vessels leading to an accelerated movement within the free vessels. At the beginning of the eighteenth century, a defender of this concept was the Italian physician Lorenzo Bellini (1643–1704). Herman Boerhaave (1668–1738), a Dutch physician, also thought that increased heartbeats were the source of the accelerated circulation and fever. In 1744, François Boissier de Sauvages de Lacroix (1706–1767), while translating in French the book on “haemastatic” written by Stephen Hales (1677–1761), added his personal view on fever, confirming the prevailing concept that inflammation was associated with increased blood flow. Thanks to scientists and doctors such as John Davy (1790–1868) in the United Kingdom who made the first sets of temperature measurements in different humans and in different environments (1816–1818), Antoine Becquerel (1852–1908) in France who invented the pyrometer to measure human temperature (1835), Thomas Clifford Allbutt (1836–1925) who invented the clinical thermometer (1866), and Reinhold August Wunderlich