Lactoferrin as a Natural Modulator of Immunity and Iron Homeostasis: A Review of Current Knowledge

Background Lactoferrin is an iron-binding glycoprotein found in secretions and neutrophil granules that regulates iron availability in conjunction with host defense. Furthermore, it modulates innate and adaptive immune responses, and affects iron handling during inflammation. Consequently, there is renewed interest in lactoferrin because of its potential therapeutic applications in iron deficiency, inflammatory disorders, and infectious diseases. Summary This review summarizes the current knowledge regarding lactoferrin as a modulator of immunity and iron homeostasis, with an emphasis on recent experimental and clinical findings. Key results indicate that lactoferrin regulates NF-κB-mediated inflammation and the IL-6-hepcidin-ferroportin pathway, both of which are central to iron-restricted erythropoiesis. This review details how lactoferrin influences cytokine signaling, leukocyte function, and mucosal-microbiota interactions, all of which are relevant to iron sequestration and intestinal iron handling. Clinically, studies support the efficacy and tolerability of lactoferrin in iron deficiency anemia and anemia of inflammation, with outcomes varying according to the formulation, dosing, and duration. This review identifies the need for standardized biomarkers and harmonized endpoints for future research. Key Messages Lactoferrin may influence immunity and iron availability in inflammatory anemia. Key pathways: NF-κB signalling and IL-6-hepcidin-ferroportin axis. Clinical results show that lactoferrin can improve hematological indices and shows good overall tolerability Evidence derives from high-risk-of-bias or very small studies. Therefore, there is a need for improved clinical trials with standardized endpoints and biomarkers.