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Altered Iron Metabolism Is Part of the Choroid Plexus Response to Peripheral Inflammation
F. Marques, A. M. Falcao, J. C. Sousa, G. Coppola, D. Geschwind, N. Sousa, M. Correia-Neves and J. A. Palha
Life and Health Sciences Research Institute (ICVS) (F.M., A.M.F., J.C.S., N.S., M.C.-N., J.A.P.), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal; and Program in Neurogenetics (G.C., D.G.), Department of Neurology, David Geffen School of Medicine-University of California Los Angeles, Los Angeles, California 90095

Address all correspondence and requests for reprints to: Joana Almeida Palha, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal. E-mail: japalha@ecsaude.uminho.pt.

Iron is essential for normal cellular homeostasis but in excess promotes free radical formation and is detrimental. Therefore, iron metabolism is tightly regulated. Here, we show that mechanisms regulating systemic iron metabolism may also control iron release into the brain at the blood-choroid plexus-cerebrospinal fluid (CSF) barrier. Intraperitoneal administration of lipopolysaccharide (LPS) in mice triggers a transient transcription of the gene encoding for hepcidin, a key regulator of iron homeostasis, in the choroid plexus, which correlated with increased detection of pro-hepcidin in the CSF. Similarly, the expression of several other iron-related genes is influenced in the choroid plexus by the inflammatory stimulus. Using primary cultures of rat choroid plexus epithelial cells, we show that this response is triggered not only directly by LPS but also by molecules whose expression increases in the blood in response to inflammation, such as IL-6. Intracellular conveyors of these signaling molecules include signal transducer and activator of transcription 3, which becomes phosphorylated, and SMAD family member 4, whose mRNA levels increase soon after LPS administration. This novel role for the choroid plexus-CSF barrier in regulating iron metabolism may be particularly relevant to restrict iron availability for microorganism growth, and in neurodegenerative diseases in which an inflammatory underlying component has been reported.

New Test Measures Hepcidin, Can Help Diagnose Anaemias and Iron Disorders

NEW YORK -- August 11, 2008 -- Researchers have developed the first method to measure the hormone hepcidin. This new blood test will help clinicians manage chronic conditions such as anaemias and iron overload diseases. The report appears in the online August issue of Blood.

The new test will directly measure hepcidin, offering more information to clinicians to help diagnose conditions and monitor the levels of this important hormone in their patients, leading to more efficient management of these chronic diseases.


"We developed and validated the first serum for hepcidin, the principal iron-regulatory hormone that has been very difficult to measure," the authors wrote.


Serum hepcidin concentrations in 24 healthy subjects correlated well with their urinary hepcidin (r = 0.82). Serum hepcidin appropriately correlated with serum ferritin (r = 0.63), reflecting the regulation of both protein by iron stores.


Expected alterations in hepcidin levels were observed in a variety of clinical conditions associated with iron disturbances. Serum ]hepcidin concentrations were undetectable or low in patients with iron deficiency anaemia (ferritin <10 ng/mL), iron-depleted HFE haemochromatosis, and juvenile haemochromatosis.


Serum hepcidin concentrations were high in patients with inflammation (C-reactive protein >10mg/dL), multiple myeloma, or chronic kidney disease.


"The new serum hepcidin yields accurate and reproducible measurements that appropriately reflect physiologic, pathologic, and genetic influences, and is informative about the aetiology of iron disorders," said the authors.


SOURCE: University of California Los Angeles

Serum hepcidin concentrations were high in patients with inflammation (C-reactive protein >10mg/dL)

The other side of the equation is anemia. When people with hemochromatosis get phlebotomized they often get into a slightly anemic state and become "iron avid". There body seems to grab and store the iron away somewhere, maybe as a response. Ferritin gets low, but the saturation can go higher again. At that point chelation may be necessary?

shye wrote:also Bethr
if i recall my basic bio, isn't the spleen where the old red blood cells get broken down and then residue sent out (via bile?), and what is needed (the iron) is recycled to make new RBC(in the marrow)?
So, without a spleen , where is the breakdown done? and maybe it is not as efficient, so you somehow put the iron, or some of it, in the wrong place (compounding any problems from the hemachromatosis alone)??

Trent wrote:I phoned my doctor today and the nurse told me that I have CYS282Tyr mutation in the HLA-H gene.

How does this fit in with the scheme of high iron as on here? I will se my doctor on Tuesday about phlebotomy. Is this still relevant?

Cece wrote:I am looking at my blood test from a few weeks ago. The only iron-related test included was Ferritin, which came back at 55 (range 10-120 ng/ml). I have to read back through this thread some...would the other tests be tsat and iron to give a more complete picture?