The Anemia Associated With Chronic Infection

Cartwright, G. E.; Lauritsen, Marjorie; Humphreys, Stewart R.; Jones, Peter J H; Merrill, I. M.; Wintrobe, M. M.

doi:10.1126/science.103.2664.72

Cited by 46 publications

(24 citation statements)

References 7 publications

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“…The anemia of the acute phase response was first observed during inflammation and disease progression by Cartwright in 1946 (108). Here, an enlargement of tissue ferritin pools was seen to be preceded by a marked increase of hepatic and spleen ferritin mRNA translation and subsequent ferritin gene transcription (109).…”

Section: B Ferritin Translational Control: Links To App and Asyn Mrnmentioning

confidence: 99%

Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases

Cahill

Lahiri

Huang

et al. 2009

Biochimica et Biophysica Acta (BBA) - General Subjects

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Summary Recent studies that alleles in the hemochromatosis gene may accelerate the onset of Alzheimer's disease (AD) by five years have validated interest in the model in which metals (particularly iron) accelerate disease course. Biochemical and biophysical measurements demonstrated the presence of elevated levels of neurotoxic copper, zinc and iron in the brains of AD patients. Intracellular levels of amyloid precursor protein (APP) holoprotein were shown to be modulated via iron by a mechanism that is similar to the translation control of the ferritin L- and H mRNAs by Iron-responsive Element (IRE) RNA stem loops in their 5′untranslated regions (5′UTRs). Recently, we reported a putative IRE-like sequence to be present in the 5′UTR of the Parkinson's disease (PD) specific alpha synuclein (ASYN) transcript. ASYN encodes the non-Aβ component (NAC) of amyloid plaques. The demonstration of iron-dependent translation of APP mRNA, the involvement of metals in the plaque of AD patients and of increased iron in striatal neurons in the Substantia nigra (SN) of PD patients, have each encouraged the development of metal attenuating agents and iron chelators as a major new therapeutic strategy for the treatment of these neurodegenerative diseases. In the case of AD, metal based therapeutics may ultimately prove more cost effective than the use of an amyloid vaccine as the preferred anti-amyloid therapeutic strategy to ameliorate the cognitive decline of AD patients.

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Section: B Ferritin Translational Control: Links To App and Asyn Mrnmentioning

confidence: 99%

Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases

Cahill

Lahiri

Huang

et al. 2009

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…Plasma iron is rapidly withdrawn from the circulation and is safely stored intracellularly in the form of ferritin. This redistribution limits iron availability for erythropoiesis and eventually leads to the so-called anemia of chronic disease (1). Hepcidin, a 25-amino acid peptide has been identified as the central systemic iron-regulating hormone, and its discovery has provided new insights into the molecular mechanisms underlying hypoferremia and iron retention in the reticuloendothelial system during inflammation (2)(3)(4).…”

mentioning

confidence: 99%

Sustained Submicromolar H2O2 Levels Induce Hepcidin via Signal Transducer and Activator of Transcription 3 (STAT3)

Millonig

Ganzleben

Peccerella

et al. 2012

Journal of Biological Chemistry

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Background: Hepcidin, the systemic iron regulator, is induced during inflammation and leads to low circulating and increased intracellular iron levels. Results: (Patho)physiologically relevant H 2 O 2 levels up-regulate hepcidin via STAT3 in cultured liver cells. Conclusion: Intracellular and extracellular H 2 O 2 acts similarly to IL-6 on hepcidin up-regulation and requires a functional STAT3-binding site. Significance: H 2 O 2 is an important link between inflammation and iron metabolism.

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“…Aconitase also binds to, and suppresses, translation of ferritin mRNA. Although regulation of iron (primarily sequestration) has been identified as an innate immune defense mechanism as far back as the 1940s,(Cartwright et al 1946), the role of iron regulation in adaptive immune function has not been studied extensively. Our results indicate that the genetic region encompassing ACO1 may be associated with cytokine responses to rubella vaccination and further investigation of this locus is warranted.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients

et al. 2014

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Genetic polymorphisms are known to affect responses to both viral infection and vaccination. Our previous work has described genetic polymorphisms significantly associated with variations in immune response to rubella vaccine from multiple gene families with known immune function, including: HLA, cytokine and cytokine receptor genes, and in genes controlling innate and adaptive immunity. In this study, we assessed cellular immune responses (IFNγ and IL-6) in a cohort of healthy younger individuals and performed genome wide SNP analysis on these same individuals. Here, we report the first genome-wide association study focused on immune responses following rubella vaccination. Our results indicate that rs16928280 in PTPRD (protein tyrosine phosphatase delta) and a collection of SNPs in ACO1 (encoding an iron regulatory protein) are associated with inter-individual variations in IFNγ response to rubella virus stimulation. In contrast, we did not identify any significant genetic associations with rubella-specific IL-6 response. These genetic regions may influence rubella vaccine-induced IFNγ responses and warrant further studies in additional cohorts in order to confirm these findings.

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The Anemia Associated With Chronic Infection

Cited by 46 publications

References 7 publications

Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases

Amyloid precursor protein and alpha synuclein translation, implications for iron and inflammation in neurodegenerative diseases

Sustained Submicromolar H2O2 Levels Induce Hepcidin via Signal Transducer and Activator of Transcription 3 (STAT3)

Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients

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