Immune rebalancing : the future of immunosuppression / [edited by] Diana Boraschi, Giselle Penton-Rol. -- Amsterdam, [Netherlands] : Academic Press, c2016. – (63.3165 /I33)

Contents

List of Contributors  xi

Chapter 1  Pharmacological Strategies Using Biologics as Immunomodulatory Agents

1.1  Introduction  1

1.2  From Nonspecific to Targeted Immunosuppression  2

1.3  From Immunosuppression to Immune Rebalancing  6

1.4  Conclusions  8

Acknowledgments  9

References  9

PART I  MECHANISMS OF IMMUNE-RELATED PATHOLOGIES AND THEIR CURRENT TREATMENT  13

Chapter 2  Advance in Therapies for Rheumatoid Arthritis: New Perspectives  15

2.1  Introduction  15

2.2  Rheumatoid Arthritis Management  16

2.3  New Alternatives for the Treatment of RA  24

2.4  Loss of Immune Tolerance as a Factor for RA Development: A Possible Target  24

2.5  Resolution of Inflammation  25

2.6  Challenges  29

2.7  Concluding Remarks    31

References  31

Chapter 3  Immune Based Therapies for Inflammatory Bowel Disease  37

3.1  Introduction  37

3.2  Immune Regulation in IBD  37

3.3  Current Immune Based Therapies in IBD  39

3.4  Immunomodulators  39

3.5  Biological Agents  42

3.6  Next Generation Immune Based Therapies in IBD  49

3.7  Conclusion  54

References  54

Chapter 4  Multiple Sclerosis and Neurodegenerative Diseases  63

4.1  Introduction  63

References   80

Chapter 5  Therapeutic Approaches in Allergic Diseases  85

5.1  General Aspects of Allergic Diseases  85

5.2  Modulation of Allergen-Specific Responses  88

5.3  Targeting Th2 Cytokines: IL-5, IL-4, and IL-13  92

5.4  Targeting IgE and FceRI  94

5.5  Targeting Mast Cells and Eosinophils  96

5.6  Conclusions  99

References  99

Chapter 6  Immunotherapy for Transforming Advanced Cancer into a Chronic Disease: How Far Are We?  105

6.1  Introduction: The Basic Biology of Chronic Diseases  105

6.2  The Evidence of a Transition to Chronicity  106

6.3  The Pharmacologic Consequence: Anticancer Drugs for Long-Term Use  109

6.4  The Expanding Role of Immunotherapy  110

6.5  A Methodological Consequence: The Need of Novel Approaches to Clinical Trial Design and Evaluation  113

6.6  Immune Rebalancing: The Research Agenda for the Age of Chronicity  114

References  117

PART II  BIOLOGICS AS IMMUNOSUPPRESSIVE AGENTS  121

Chapter 7  Modulation of Macrophage Activation  123

7.1  Introduction  123

7.2  An Overview on Macrophage Polarization/Activation  124

7.3  MI/M2 Skewing: Detrimental and Beneficial Consequences  128

7.4  Mechanisms of Macrophage Activation  132

7.5  Local Conditions and Cell-Cell Interactions: Other Cues in Macrophage Polarization  137

7.6  Therapeutic Applications Based on Modulation of Macrophage Polarization/Activation in the Tumor  140

7.7  Conclusions  141

Acknowledgments  143

Conflict of Interest  143

References  143

Chapter 8  Modulating Inflammatory Cytokines: IL-1  151

8.1  Introduction  151

8.2  Biologicals Targeting IL-1  154

8.3  Blocking IL-1 in Disease  155

8.4  Conclusions  163

References  163

Chapter 9  Systems Medicine of Autoimmune Diseases: From Understanding Complexity to Precision Treatments  173

9.1  Introduction  173

9.2  From Systems Biology to Systems Medicine  175

9.3  Systems Biology and the Emerging Technologies  175

9.4  Application of Emerging Technologies in Autoimmune Research  176

9.5  From Systems Medicine to Precision Medicine  183

References  183

Chapter 10  The Microbiota and Its Modulation in Immune-Mediated Disorders  191

10.1  Introduction  191

10.2  Development of the Gut Microbiota  192

10.3  Microbiota Effects on Immune Development  193

10.4  Microbiota Modulation  197

10.5  Microbiota Involvement in Prevalence and Progression Immune-Related Disease

10.6  Summary and Conclusions  211

Acknowledgements  215

References  215

Chapter 11  Natural Products: Immuno-Rebalancing Therapeutic Approaches  229

11.1  Introduction  229

11.2  Modulation of Immune Responses for Disease Prevention and Treatment  231

11.3  Traditional Medicinal Preparations have Immunoactive Properties  233

11.4  Natural Products can Influence and Modify Intersystem Interactions and Infection Resistance  234

11.5  Immunosuppression is not the Abrogation but the Rebalancing of Immune Functions  236

11.6  The Oxidant versus Antioxidant Argument does not Provide Responses but Creates Uncertainty  238

11.7  Neuroprotection/Restoration is Achievable by Natural Products  240

11.8  C-Phycocyanin/Phycocyanobilin Properties, Mechanisms and Prospects  241

11.9  Conclusions    243

References  245

Chapter 12  Nanomedicine    251

12.1  Why Nanomaterials?  251

12.2  Products on the Market or in Development  253

12.3  Suppressing Immunity: Autoimmunity and Other Cases  255

12.4  Activating Immunity: The Future of Vaccines?  258

12.5  Cancer as an Immunological Disease  260

12.6  Allergy  262

12.7  What Are We Really Using?  264

12.8  Rebalancing Exciting New Prospects and Over-Optimistic Hype  266

12.9  Acknowledgements  267

References  267

Index  275