Iron homeostasis during anemia of inflammation: a prospective study of 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 antituberculosis treatment to support hemoglobin (Hb) recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, as well as changes in inflammation and iron metabolism indices. In a 26-week prospective study, Tanzanian adults with tuberculosis (N = 18) were studied before treatment and then every 2 weeks during treatment; oral and intravenous iron tracers were administered before treatment and after intensive phase (8/12 weeks) and complete treatment (24 weeks). No iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (similar to 80%), and iron absorption was negligible (<1%). During treatment, hepcidin and interleukin-6 levels decreased similar to 70% after only 2 weeks (P < .001); in contrast, ERFE did not significantly decrease until 8 weeks (P < .05). ERFE and interleukin-6 were the main opposing determinants of hepcidin (P < .05), and greater ERFE was associated with reticulocytosis and Hb repletion (P < .01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (P < .01), indicating enhanced erythropoiesis. After treatment completion, iron absorption increased similar to 20-fold (P < .001), and Hb increased similar to 25% (P < .001). In tuberculosis-associated anemia of inflammation, our findings suggest that 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.

Automated summary

Anemia of inflammation is a common feature in tuberculosis patients, with elevated levels of erythroferrone unable to suppress hepcidin. Iron absorption remains negligible during tuberculosis treatment, but improves significantly after completion of treatment, indicating that supplementation should be considered for patients remaining anemic post-treatment.