A novel treatment of anemia of inflammation.

In this issue of Blood, van Eijk et al investigate a synthetic compound that inhibits the iron-regulatory hormone hepcidin to fight anemia of inflammation in human endotoxemia. Anemia is one of the major public health burdens. TheWorldHealth Organization estimates the prevalence of anemia at 2 billion people worldwide. Prevalence of anemia in 2010 was estimated at 32.9% in a systemic analysis of the global anemia burden from 1990 to 2010. Anemia caused 68.4 million years lived with disability. Iron deficiency anemia is the most frequent form of anemia, typically due to nutritional deficiency and characterized by intact regulation of iron homeostasis and decreased serum iron levels and tissue iron stores. Anemia of inflammation, also known as the anemia of chronic disease, is the second most common form of anemia. In anemia of inflammation, acute or chronic infections or neoplastic disease cause an immune-modulatory response in patients with an induction of cytokine expression. Cytokines, in turn, lead to an increase of the iron-regulatory hormone hepcidin. Synthesized mainly by the liver, hepcidin maintains systemic iron homeostasis by posttranslationally downregulating levels of the sole iron exporter, ferroportin. Hepcidin binds to ferroportin and causes internalization and degradation of the iron exporter. As the 3 sites of ferroportin expression are duodenal enterocytes, hepatocytes, and reticuloendothelial macrophages, dietary iron absorption and iron release from tissue stores is inhibited. Anemia of inflammation ultimately ensues. Anemia of inflammation is frequent in hospitalized patients. A secondary retrospective analysis of a prospective study of 39 309 patients from 28 European nations on preoperative anemia revealed that 26.5% of women and 31.1% of men were anemic. If these patients undergo surgery, preoperative anemia is a risk factor associated with higher in-hospitalmortality, longer stay in the hospital, and higher frequency of postoperative admission to the intensive care unit compared with patients without preoperative anemia. Fighting anemia therefore is of high clinical relevance and critical, independent of age and country of residence. To date, therapeutic options for anemia of inflammation include treatment of the underlying disease, blood transfusions, intravenous iron supplementation, or erythropoietin, if applicable. Because hepcidin is induced in anemia of inflammation, researchers have tried for several years to identify a means to target and inhibit hepcidin. If hepcidin expression can be inhibited or biologically inactivated, the iron Effects of placebo or lexaptepid treatment on inflammatory-mediated hepcidin induction and systemic iron homeostasis. With placebo, acute or chronic inflammations as well as neoplastic disease cause an induction of cytokines. Cytokines, in turn, induce the expression of the iron-regulatory hormone hepcidin. Hepcidin degrades the iron-export channel ferroportin, so that hypoferremia develops. Erythropoiesis and hemoglobin levels decrease. Anemia of inflammation ensues. Patients treated with lexaptepid show the same induction of cytokines. Hepcidin is induced but bound by lexaptepid. The hepcidin-lexaptepid complex is biologically inactive and prevents hypoferremia. Therefore, lexaptepid might be a possible treatment of anemia of inflammation. The effects on erythropoiesis and hemoglobin levels have yet to be determined in clinical trials. TSAT, transferrin saturation. Professional illustration by XavierStudio.