Iron out-of-balance: a risk factor for acute and chronic diseases.

The numerous acute and chronic diseases associated with excessive/misplaced iron are categorized in this review in the following sections: 1) iron, by itself, can initiate the disease; 2) iron can be a cofactor in promoting the disease; 3) iron deposits are observed in disease-associated tissue sites; 4) body iron loading is associated with above normal incidence of the disease; and 5) maternal antibodies can impair fetal iron metabolism. Also discussed is the anomalous condition in which persons whose macrophages are low in iron are resistant to microbial pathogens that require iron loaded macrophages for in vivo growth. Thus, hemochromatotic mutations have apparently had survival value during outbreaks of tuberculosis, plague and typhoid fever.