The Iron Dysregulation and Dormant Microbes Hypothesis for Chronic, Inflammatory Diseases
Biol. Rev. (2018), 93, pp. 1518–1557. 1518 doi: 10.1111/brv.12407 No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases Douglas B. Kell1,2,3,∗ and Etheresia Pretorius3 1School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, Lancs M1 7DN, U.K. 2The Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, Lancs M1 7DN, U.K. 3Department of Physiological Sciences, Stellenbosch University, Stellenbosch Private Bag X1, Matieland, 7602, South Africa ABSTRACT Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer’s, Parkinson’s), vascular (e.g. atherosclerosis, pre-eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially ‘external’ causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress-induced iron dysregulation, and (ii) its ability to awaken dormant, non-replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens.
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