Elevated Serum Ferritin in Inflammatory & Degenerative Diseases -- 'Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells', Metallomics 2014

"Serum ferritin" presents a paradox, as the iron storage protein ferritin is not synthesised in serum yet is to be found there. Serum ferritin is also a well known inflammatory marker, but it is unclear whether serum ferritin reflects or causes inflammation, or whether it is involved in an inflammatory cycle. We argue here that serum ferritin arises from damaged cells, and is thus a marker of cellular damage. The protein in serum ferritin is considered benign, but it has lost (i.e. dumped) most of its normal complement of iron which when unliganded is highly toxic. The facts that serum ferritin levels can correlate with both disease and with body iron stores are thus expected on simple chemical kinetic grounds. Serum ferritin levels also correlate with other phenotypic readouts such as erythrocyte morphology. Overall, this systems approach serves to explain a number of apparent paradoxes of serum ferritin, including (i) why it correlates with biomarkers of cell damage, (ii) why it correlates with biomarkers of hydroxyl radical formation (and oxidative stress) and (iii) therefore why it correlates with the presence and/or severity of numerous diseases. This leads to suggestions for how one might exploit the corollaries of the recognition that serum ferritin levels mainly represent a consequence of cell stress and damage....

Some diseases in which serum ferritin levels correlate with the presence or severity of disease...

A selection of diseases in which their presence or severity is known to be related to serum ferritin levels. The table purposely excludes classic ‘iron overload’ diseases such as haemochromatosis, thalassaemia and myelodysplastic syndrome. It also excludes syndromes such as Alzheimer's disease and Parkinson's disease, where a great many papers show dysregulation of iron metabolism in brain tissue but where there is very little work in serum....

Acute respiratory distress syndrome
Amyotrophic lateral sclerosis
Atherosclerosis
Cancer
Cirrhosis of the liver
Coronary artery disease
Diabetes mellitus, type 2
Hypertension
Metabolic syndrome
Multiple sclerosis
Myocardial infarction
Non-alcoholic fatty liver disease
Preeclampsia
Rheumatoid arthritis
Sepsis/SIRS
Stroke
Systemic lupus erythematosus

...Summarising remarks

Although serum ferritin is widely seen as an inflammatory biomarker, our understanding of its role as an intracellular iron storage protein gives no explanation of why it should even exist in serum. The view summarised here is that serum ferritin leaks from damaged cells, losing most of its iron on the way, and leaving that iron in an unliganded form that can impact negatively on health. This unliganded iron can of course stimulate further cell damage.17 This overall view serves straightforwardly to explain the following, known observations.
(1) Serum ferritin exists, despite the fact that ferritin is not synthesised in the serum.
(2) Serum ferritin lacks most of the iron it contained when intracellular.
(3) The intracellular ferritin must have ‘dumped’ its unliganded iron somewhere, where it can participate in Haber–Weiss and Fenton reactions, creating hydroxyl radicals and consequent further cellular damage.
(4) The serum ferritin protein is itself considered benign.139
(5) Yet the level of serum ferritin correlates with numerous inflammatory and degenerative diseases...."
learn more/full paper: http://pubs.rsc.org/en/content/articlehtml/2014/mt/c3mt00347g
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