A Review on Iron Homeostasis and Anaemia in Pulmonary Tuberculosis

The paper discussed iron homeostasis and anaemia in pulmonary tuberculosis. Iron (Fe) is one of the most abundant elements in the earth’s crust and an essential nutrient for almost all known organisms. It is able to receive and release electrons during conversion from Fe (II) to Fe (III) and plays a major role in DNA production and in energy generation. A system of highly regulated mechanisms is in place to control iron homeostasis. Regulation occurs at both the systemic and cellular levels and influences a number of iron-associated proteins. The iron regulatory protein, hepcidin, plays an important role in the mechanisms responsible for AI and the inflammation-mediated alteration of iron homeostasis. Specifically, hepcidin binds to and degrades the iron export protein ferroportin and down-regulates expression of the iron importer DMT1.Since hepcidin transcription is induced by the pro-inflammatory cytokine, interleukin-6 (IL-6), inflammation leads to a reduction in iron absorption and causes iron to be sequestered in macrophages and enterocytes.The inflammatory cytokines that are released upon innate recognition of a pathogen induce changes in plasma concentrations of other proteins. This phenomenon is referred to as the acute phase response (APR) and the affected proteins are considered acute phase proteins (APPs). The iron homeostasis proteins ferritin, transferrin and hepcidin are considered APPs, as are C-reactive protein (CRP) and alpha-1-antichymotrypsin (ACT), both of which are often utilized in studies as markers of inflammation. In the context of infection, iron’s limited availability within the human body and its physiological importance to both hosts and microbes make it a valuable commodity. Many microbes depend on host-acquired iron and, in response; hosts use their complex system of iron regulation to modify their iron metabolism and restrict iron availability. Evidence links iron with PTB pathogenesis both from the perspective of the pathogen and the host. Upon infection, host immune recognition of Mtb induces a pro-inflammatory reaction that restricts iron access. Most strikingly, a pattern of altered host iron status characterized by high ferritin, low transferrin, and low hemoglobin has been identified as a risk factor for progression to PTB. Decreasing iron availability (regardless of the mechanism) reduces Mtb growth, and addition of iron to Mtb almost always enhances growth.