5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION
-
Manfred Nairz
Abstract
A dynamic interplay between the host and pathogen determines the course and outcome of infections. A central venue of this interplay is the struggle for iron, a micronutrient essential to both the mammalian host and virtually all microbes. The induction of the ironregulatory hormone hepcidin is an integral part of the acute phase response. Hepcidin switches off cellular iron export via ferroportin-1 and sequesters the metal mainly within macrophages, which limits the transfer of iron to the serum to restrict its availability for extracellular microbes. When intracellular microbes are present within macrophages though, the opposite regulation is initiated because infected cells respond with increased ferroportin-1 expression and enhanced iron export as a strategy of iron withdrawal from engulfed bacteria. Given these opposing regulations, it is not surprising that disturbances of mammalian iron homeostasis, be they attributable to genetic alterations, hematologic conditions, dietary iron deficiency or unconsidered iron supplementation, may affect the risk and course of infections. Therefore, acute, chronic or latent infections need to be adequately controlled by antimicrobial therapy before iron is administered to correct deficiency. Iron deficiency per se may negatively affect growth and development of children as well as cardiovascular performance and quality of life of patients. Of note, mild iron deficiency in regions with a high endemic burden of infections is associated with a reduced prevalence and a milder course of certain infections which may be traced back to effects of iron on innate and adaptive immune function as well as to restriction of iron for pathogens. Finally, absolute and functional causes of iron deficiency need to be differentiated, because in the latter form, oral iron supplementation is inefficient and intravenous application may adversely affect the course of the underlying disease such as a chronic infection. This chapter summarizes our current knowledge on the regulation of iron metabolism and the interactions between iron and the immune response against microbes. Moreover, some of the unanswered questions on the association of iron administration and infections are addressed.
Abstract
A dynamic interplay between the host and pathogen determines the course and outcome of infections. A central venue of this interplay is the struggle for iron, a micronutrient essential to both the mammalian host and virtually all microbes. The induction of the ironregulatory hormone hepcidin is an integral part of the acute phase response. Hepcidin switches off cellular iron export via ferroportin-1 and sequesters the metal mainly within macrophages, which limits the transfer of iron to the serum to restrict its availability for extracellular microbes. When intracellular microbes are present within macrophages though, the opposite regulation is initiated because infected cells respond with increased ferroportin-1 expression and enhanced iron export as a strategy of iron withdrawal from engulfed bacteria. Given these opposing regulations, it is not surprising that disturbances of mammalian iron homeostasis, be they attributable to genetic alterations, hematologic conditions, dietary iron deficiency or unconsidered iron supplementation, may affect the risk and course of infections. Therefore, acute, chronic or latent infections need to be adequately controlled by antimicrobial therapy before iron is administered to correct deficiency. Iron deficiency per se may negatively affect growth and development of children as well as cardiovascular performance and quality of life of patients. Of note, mild iron deficiency in regions with a high endemic burden of infections is associated with a reduced prevalence and a milder course of certain infections which may be traced back to effects of iron on innate and adaptive immune function as well as to restriction of iron for pathogens. Finally, absolute and functional causes of iron deficiency need to be differentiated, because in the latter form, oral iron supplementation is inefficient and intravenous application may adversely affect the course of the underlying disease such as a chronic infection. This chapter summarizes our current knowledge on the regulation of iron metabolism and the interactions between iron and the immune response against microbes. Moreover, some of the unanswered questions on the association of iron administration and infections are addressed.
Chapters in this book
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 19 ix
- Contents xiii
- Contributors to Volume 19 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. METALS IN MEDICINE: THE THERAPEUTIC USE OF METAL IONS IN THE CLINIC 1
- 2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION? 17
- 3. IRON CHELATION FOR IRON OVERLOAD IN THALASSEMIA 49
- 4. IRONING OUT THE BRAIN 87
- 5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION 123
- 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION 157
- 7. BUILDING A TROJAN HORSE: SIDEROPHORE-DRUG CONJUGATES FOR THE TREATMENT OF INFECTIOUS DISEASES 181
- 8. DEVELOPING VANADIUM AS AN ANTIDIABETIC OR ANTICANCER DRUG: A CLINICAL AND HISTORICAL PERSPECTIVE 203
- 9. CHROMIUM SUPPLEMENTATION IN HUMAN HEALTH, METABOLIC SYNDROME, AND DIABETES 231
- 10. MANGANESE: ITS ROLE IN DISEASE AND HEALTH 253
- 11. COBALT-SCHIFF BASE COMPLEXES: PRECLINICAL RESEARCH AND POTENTIAL THERAPEUTIC USES 267
- 12. COPPER DEPLETION AS A THERAPEUTIC STRATEGY IN CANCER 303
- 13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC 331
- 14. CHEMICAL AND CLINICAL ASPECTS OF METAL-CONTAINING ANTIDOTES FOR POISONING BY CYANIDE 359
- SUBJECT INDEX 393
Chapters in this book
- Frontmatter i
- About the Editors v
- Historical Development and Perspectives of the Series vii
- Preface to Volume 19 ix
- Contents xiii
- Contributors to Volume 19 xix
- Titles of Volumes 1–44 in the Metal Ions in Biological Systems Series xxiii
- Contents of Volumes in the Metal Ions in Life Sciences Series xxv
- 1. METALS IN MEDICINE: THE THERAPEUTIC USE OF METAL IONS IN THE CLINIC 1
- 2. SMALL MOLECULES: THE PAST OR THE FUTURE IN DRUG INNOVATION? 17
- 3. IRON CHELATION FOR IRON OVERLOAD IN THALASSEMIA 49
- 4. IRONING OUT THE BRAIN 87
- 5. INFECTIONS ASSOCIATED WITH IRON ADMINISTRATION 123
- 6. IRON OXIDE NANOPARTICLE FORMULATIONS FOR SUPPLEMENTATION 157
- 7. BUILDING A TROJAN HORSE: SIDEROPHORE-DRUG CONJUGATES FOR THE TREATMENT OF INFECTIOUS DISEASES 181
- 8. DEVELOPING VANADIUM AS AN ANTIDIABETIC OR ANTICANCER DRUG: A CLINICAL AND HISTORICAL PERSPECTIVE 203
- 9. CHROMIUM SUPPLEMENTATION IN HUMAN HEALTH, METABOLIC SYNDROME, AND DIABETES 231
- 10. MANGANESE: ITS ROLE IN DISEASE AND HEALTH 253
- 11. COBALT-SCHIFF BASE COMPLEXES: PRECLINICAL RESEARCH AND POTENTIAL THERAPEUTIC USES 267
- 12. COPPER DEPLETION AS A THERAPEUTIC STRATEGY IN CANCER 303
- 13. METAL COMPOUNDS IN THE DEVELOPMENT OF ANTIPARASITIC AGENTS: RATIONAL DESIGN FROM BASIC CHEMISTRY TO THE CLINIC 331
- 14. CHEMICAL AND CLINICAL ASPECTS OF METAL-CONTAINING ANTIDOTES FOR POISONING BY CYANIDE 359
- SUBJECT INDEX 393
