Iron homeostasis during anemia of inflammation: a prospective study in patients with tuberculosis

Anemia of inflammation is a hallmark of tuberculosis. Factors controlling iron metabolism during anemia of inflammation and its resolution are uncertain. Whether iron supplements should be given during anti-tuberculosis treatment to support Hb recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, and changes in inflammation and iron metabolism indices. In a 26-wk prospective study, Tanzanian adults with tuberculosis (n=18) were studied before treatment and then every two weeks during treatment; oral and intravenous iron tracers were administered before treatment, after intensive phase (8/12 wk) and complete treatment (24 wk); no iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (~80%) and iron absorption was negligible (<1%). During treatment, hepcidin and IL-6 decreased ~70% after only 2 wk (p<0.001); in contrast, ERFE did not significantly decrease until 8 wk (p<0.01). ERFE and IL-6 were the main opposing determinants of hepcidin (p<0.05) and greater ERFE was associated with reticulocytosis and hemoglobin (Hb) repletion (p<0.01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (p<0.01) indicating enhanced erythropoiesis. After treatment completion, iron absorption increased ~20-fold (p<0.001); Hb increased ~25% (p<0.001). In tuberculosis-associated anemia of inflammation, our findings suggest elevated ERFE is unable to suppress hepcidin and iron absorption is negligible. During treatment, as inflammation resolves, ERFE may remain elevated, contributing to hepcidin suppression and Hb repletion. Iron is well-absorbed only after tuberculosis treatment and supplementation should be reserved for patients remaining anemic after treatment. (ClinicalTrials.gov Identifier:NCT02176772).

Aspects of the pathogenesis of anemia in cancer patients

Anemia is considered one of the manifistations of many neoplasms affecting the overall survival and reducing the quality of life of patients. The prevalence of anemia varies from 20 to 90% depending on the nosology, the stage of the disease, antitumor treatment. The pathogenesis of anemia in cancer patients is complex. Among pathogenetic factors, such factors are distinguished as tumor infiltration of the bone marrow by malignant cells, inhibition of erythroid growth by cytokines of inflammation, decreased sensitivity of receptors to erythropoietin and its production, increased levels of hepcidin, defects of nutrition, increased deposition and sequestration of blood cells in the spleen, excessive bone fibrosis, hemorrhagic syndrome, antitumor therapy. The article presents the pathogenesis of anemia in oncological disease with a detailed description of the suppressive effect on hematopoiesis of a number of proinflammatory cytokines (interleukin-1, interleukin-6, tumor necrosis factor-, interferon-) produced by cells of the immune system. The mechanism of influence of cytokines on erythropoiesis, synthesis of erythropoietin as well as on the enhancement of hepcidin production in the body is presented in detail. The article also describes the mechanism of impairment of iron kinetics in the body in patients with cancer and subsequent development of functional deficiency. This review of the literature contains up-to-date information about the factors involved in the pathogenesis of anemia in cancer patients, understanding of which will allow the clinical physician to choose a rational way of pathogenetic or substitution correction of anemic syndrome, taking into account the personalized approach to treatment and prevention, especially in patients receiving surgical, chemotherapy, radiation treatment.