Lactoferrin in Aseptic and Septic Inflammation

Abstract

Lactoferrin (Lf), a cationic glycoprotein able to chelate two ferric irons per molecule, is synthesized by exocrine glands and neutrophils. Since the first anti-microbial function attributed to Lf, several activities have been discovered, including the relevant anti-inflammatory one, especially associated to the down-regulation of pro-inflammatory cytokines, as IL-6. As high levels of IL-6 are involved in iron homeostasis disorders, Lf is emerging as a potent regulator of iron and inflammatory homeostasis. Here, the role of Lf against aseptic and septic inflammation has been reviewed. In particular, in the context of aseptic inflammation, as anemia of inflammation, preterm delivery, Alzheimer’s disease and type 2 diabetes, Lf administration reduces local and/or systemic inflammation. Moreover, Lf oral administration, by decreasing serum IL-6, reverts iron homeostasis disorders. Regarding septic inflammation occurring in Chlamydia trachomatis infection, cystic fibrosis and inflammatory bowel disease, Lf, besides the anti-inflammatory activity, exerts a significant activity against bacterial adhesion, invasion and colonization. Lastly, a critical analysis of literature in vitro data reporting contradictory results on the Lf role in inflammatory processes, ranging from pro- to anti-inflammatory activity, highlighted that they depend on cell models, cell metabolic status, stimulatory or infecting agents as well as on Lf iron saturation degree, integrity and purity.

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

“…In this scenario, molecules able to boost cytotoxic immune components as well as to shut down pro-tumorigenic inflammatory mediators could be considered potentially good candidates as adjuvant to standard anti-cancer therapies. In this regard, Lf has proven to potentiate adaptive immune response as well as to act as a potent anti-inflammatory agent [17,102,186]. Even if the molecular mechanism is still under debate, the findings that both hLf and bLf are able to enter inside host nucleus [97,101] and to bind human DNA have shed some light on the possible mechanism by which the glycoprotein can modulate gene expression, thus exerting its anti-inflammatory activity [17].…”

“…This different feature reflects distinct functions of the considered proteins: indeed, sTf acts as a cargo for iron transport not only into cells [12] but also in the blood, a district that it is usually characterized by pH values in a narrow neutral range (7.2-7.4) [13], while Lf often exerts its role at inflamed and infected sites, where pH can reach acidic values. Indeed, Lf shares its anti-microbial, antifungal, antiviral, and anti-parasitic activities with ovo-Tf [14,15], whereas it possesses unique features as an anti-inflammatory, immunomodulatory, and anti-cancer molecule [16][17][18]. Moreover, it is emerging as a fundamental regulator of cellular and systemic iron homeostasis [19,20].…”

Editorial to Special Issue—Anti-Inflammatory Activity of Natural Products

“…A review article by Lepanto et al [23] compiled information on the role of lactoferrin, a cationic glycoprotein able to chelate two ferric irons per molecule and synthesized by exocrine glands and neutrophils, against aseptic (anemia of inflammation, preterm delivery, Alzheimer's disease and diabetes type 2) and septic inflammation (Chlamydia trachomatis infection, cystic fibrosis and inflammatory bowel disease). The authors [23] reported that orally administered lactoferrin decreases the serum IL-6, which means a reversion of iron homeostasis disorders.…”

“…A review article by Lepanto et al [23] compiled information on the role of lactoferrin, a cationic glycoprotein able to chelate two ferric irons per molecule and synthesized by exocrine glands and neutrophils, against aseptic (anemia of inflammation, preterm delivery, Alzheimer's disease and diabetes type 2) and septic inflammation (Chlamydia trachomatis infection, cystic fibrosis and inflammatory bowel disease). The authors [23] reported that orally administered lactoferrin decreases the serum IL-6, which means a reversion of iron homeostasis disorders. Nevertheless, after the revision made by the authors, they also found contradictory in vitro results, ranging from pro-to anti-inflammatory activity of lactoferrin depending on the cell models used, cell metabolic status, stimulatory or infecting agents and finally to the iron saturation degree of lactoferrin, its integrity and purity [23].…”

“…The authors [23] reported that orally administered lactoferrin decreases the serum IL-6, which means a reversion of iron homeostasis disorders. Nevertheless, after the revision made by the authors, they also found contradictory in vitro results, ranging from pro-to anti-inflammatory activity of lactoferrin depending on the cell models used, cell metabolic status, stimulatory or infecting agents and finally to the iron saturation degree of lactoferrin, its integrity and purity [23].…”