Review: Effects of iron overload on the immune system

Iron and irs binding proteins have immunoregulatory properties, and shiftin g of immunoregulatory balances by iron excess or deficiency may produce sev ere, deleterious physiological effects. Effects of iron overload include de creased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of l ymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surfac e markers, influencing the expansion of different T-cell subsets, and affec ting immune cell functions can be demonstrated in vitro and in vivo. The po or ability of lymphocytes to sequester excess iron in Ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron o verload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity: nu mbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratio s, impairs the generation of cytotoxic T cells, and alters immunoglobulin s ecretion when compared to treated hereditary hemochromatosis patients or co ntrols. A correlation has recently been found between low CD8+ lymphocyte n umbers, liver damage associated with HCV positivity, and severity of iron o verload in beta-thalassemia major patients. Iron overload, with its associa ted increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is as sociated with suppressed functions of the complement system (classic or alt ernative types). High plasma ferritin content in patients with chronic, dif fuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the de velopment of anti-ferritin antibodies with the production of circulating im mune complexes. Increased body stores of iron in various clinical situation s may tip the immunoregulatory balance unfavorably to allow increased growt h rates of cancer cells and infectious organisms, and complicate the clinic al management of preexisting acute and chronic diseases.