| Popis: |
Anemia of chronic disease (ACD) may also be referred to as anemia of inflammation and this develops in subjects with diseases involving acute or chronic immune activation. Anemia, which could be described as an immunopathological feature in most established infection, may also be a consequence of host response to invading pathogens. Infections with pathogens normally activate macrophages triggering a strong cytokine production among which are tumor necrosis factor (TNF), γ-interferon (IFN-γ) and nitric oxide (NO). The immune response mounted against such infections is required for parasite clearance but its persistence can cause collateral damage to the host with occurrence of anemia as the major pathology. Inflammation results as a part of this natural immune response. The inflammation triggers the release of chemicals that signal the iron regulation mechanism to adopt a defense mode. Thus this type of anemia is usually characterised by an imbalance between erythrophagocytosis and erythropoiesis, which is linked to, perturbed iron (Fe) homeostasis including altered Fe sequestration and recycling by macrophages and/or sustained and overproduction of NO. The exact mechanism of ACD is not fully understood although studies suggest that the syndrome may partly be due to the influence of hepcidin production on iron metabolism. Moreover complex relationships between Fe and NO has been demonstrated and may be linked to iron deficient anemia during infection. Both iron and nitric oxide play important roles in the progression and outcome of ACD essentially through the promotion of free radical generation and/or altered homeostasis. Increased iron status may promote free hydroxyl radical generation in cellular systems and thus potentiate cellular damage. Subsequently continuous and sustained production of nitric oxide resulting from persistent infection could contribute to oxidative damage via the formation of peroxynitrite, a very reactive free radical, which may promote lipid peroxidation of key biomolecules and membranes. It should also be noted that production of nitric oxide during infection episodes affects iron metabolism and vice versa. This suggest that a delicate homeostatic balance exist between iron and nitric oxide in living cells such that a disruption or perturbation of this strictly regulated balance would physiologically affect the cellular system. The fact that strong link that has been demonstrated between iron and nitric oxide indicates that the duo play crucial physiological roles in cellular processes. |
