Anemia inflamatoria

MARROW RESPONSES TO AGING AND INFLAMMATION

Anemia of Inflammation
Cindy N. Roy1
1Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD

Inflammation arising from various etiologies, including infection, autoimmune disorders, chronic diseases, and aging, can promote anemia. The anemia of inflammation (AI) is most often normocytic andnormochromic and is usually mild. Characteristic changes in systemic iron handling, erythrocyte production, and erythrocyte life span all contribute to AI. The preferred treatment is directed at the underlying disease. However, when the inflammatory insult is intractable, or the cause has not been diagnosed, there are limited options for treatment of AI. Because anemia is a comorbid condition that isassociated with poor outcomes in various chronic disease states, understanding its pathogenesis and developing new tools for its treatment should remain a priority. Hepcidin antimicrobial peptide has taken center stage in recent years as a potent modulator of iron availability. As the technology for quantitative hepcidin analysis improves, hepcidin’s role in various disease states is also beingrevealed. Recent insights concerning the regulatory pathways that modify hepcidin expression have identified novel targets for drug development. As the field advances with such therapeutics, the analysis of the impact of normalized hemoglobin on disease outcomes will confirm whether anemia is a reversible independent contributor to the morbidity and mortality associated with inflammatory diseases.Clinical Presentation
Anemia of inflammation (AI) can occur during infections with a microbial pathogen, including bacterial, viral, or yeast infections, or it can occur in the context of autoimmune disorders such as systemic lupus erythematosus or rheumatoid arthritis. AI may also result from chronic disease states with low-grade inflammatory activity, such as cancer, chronic kidney disease, orcongestive heart failure. Even the pro-inflammatory state of aging, independent of disease, may result in anemia that is postulated to have a similar pathogenesis. AI is most commonly described as a normocytic, normochromic anemia, but it can become microcytic and hypochromic as the disease progresses.1 Reticulocytosis is not usually observed. Characteristic changes in systemic iron distribution developsuch that the serum iron concentration and transferrin saturation are low, while macrophage iron stores remain replete. Hypoferremia and sequestration of iron in tissue macrophages are thought to protect the host by limiting the availability of this micronutrient, which is required for the proliferation of most microbial pathogens. A “blunted” erythropoietin (Epo) response has also been described.In some disease contexts, Epo production is not sufficiently increased relative to the severity of the anemia. Alternatively, the blunted Epo response has been described as the inability of the erythron to respond to available Epo. Finally, decreased erythrocyte life span has been reported in some patient groups with AI. These features of AI suggest that the immune response promotes ironsequestration, but also inhibits the production and survival of erythrocytes.2 While many of these features have been observed in a number of different patient populations, there is some variability in clinical expression that may be related to the duration or severity of the inflammation or to differential expression of various pro-inflammatory cytokines that direct the inflammatory response. It is conceivablethat the variation in the “cytokine profile” across disease states may lead to variations in the mechanisms that restrict erythropoiesis

or promote turnover of erythrocytes and therefore affect the presentation of AI.

Molecular Pathophysiology

The Normal Erythrocyte Life Cycle
Erythroid precursors at multiple developmental stages form physical interactions with a central macrophage...