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 (∼80%), and
iron absorption was negligible (<1%). During treatment,
hepcidin and
interleukin-6 levels decreased ∼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 ∼20-fold (P< .001), and Hb increased ∼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. This trial was registered at www.clinicaltrials.gov as #NCT02176772.