Lactoferrin: A Natural Glycoprotein Involved in Iron and Inflammatory Homeostasis

Abstract

Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH). Consequently, bLf inhibits intracellular iron overload, an unsafe condition enhancing in vivo susceptibility to infections, as well as anemia of inflammation (AI), re-establishing IIH. In pregnant women, affected by AI, bLf oral administration decreases IL-6 and increases hematological parameters. This surprising effect is unrelated to iron supplementation by bLf (80 μg instead of 1–2 mg/day), but to its role on IIH. AI is unrelated to the lack of iron, but to iron delocalization: cellular/tissue overload and blood deficiency. BLf cures AI by restoring iron from cells to blood through Fpn up-expression. Indeed, anti-inflammatory activity of oral and intravaginal bLf prevents preterm delivery. Promising bLf treatments can prevent/cure transitory inflammation/anemia/oral pathologies in athletes.

A Comparative Study to Evaluate the Efficacy of Oral Lactoferrin Fortified Bovine Colostrum with Oral Iron in the Treatment of Iron Deficiency Anemia

“…The significant increase in Hb and SIC values post-therapy in both Group II and III (p<0.05) is in accordance with study by Paesano et al, 2006 conducted among pregnant women in Italy which reported a mean increase in Hb of 1.5 g/dL and a mean increase in SIC of 54.2 μg/Dl. 15 In the present study, a mean rise in Hb of 0.9288 g/dL and a mean rise in SIC of 18.4952 μg/dL was noted in Group II. Group III exhibited a mean rise in Hb of 1.0625 g/dL and mean rise in SIC of 17.3575 μg/dL.…”

“…Its efficacy in increasing iron parameters in pregnant women has been established in a few European studies. [14][15][16] The highest concentration of lactoferrin is found in colostrum (7 g/dL) followed by milk (1 g/dL) where it is believed to be a major source of iron for infants. 17 Lactoferrin is purified and isolated from human or cow's milk; however, recombinant lactoferrin is also available.…”

Gestational Iron Deficiency Anemia Is Not Simply a Consequence of Iron Deficiency: An Observational Study for Cofounders.

“…Furthermore, Rosa et al (39) reported that bovine lactoferrin through its antiinflammatory activity against IL-6 cures anemia of inflammation through up-regulating Fpn and transferrin receptor 1, while down-regulating ferritin and consequently inhibits intracellular iron overload with increased availability of iron for erythropoiesis…”

Медикаментозне Обмеження Доступності Іонів Заліза Для Патогенних Бактерій (Частина 1)

“…Также продемонстрировано, что галлий, используя стратегию троянского коня, вытесняет железо из структур бактериальных си-дерофоров [12]. Лактоферрин захватывает ионы железа, что приводит к снижению объема пула же-леза, доступного для патогенных бактерий [39].…”

“…Лактоферрин оказывает антибактериальное влияние за счет противодействия бактериальному синтезу высокоаффинных хелаторов ионов трех-валентного железа (сидерофоров) и ограничения доступа бактерий к ионам железа, физически свя-зывая его свободные ионы [39].…”