Lactoferrin in Treatment of Fe Deficient Anemia In Cirrhosis

Overview

Iron deficiency and altered homeostasis due to inflammation and decreased iron utilization are main factors involved in anemia in liver disease. Lactoferrin is a first line defence protein for protection against microbial infections and subsequent development of systemic disease as seen with systemic inflammatory response syndrome (SIRS) and sepsis. Lactoferrin with iron has been shown to be efficacious with anemia in chronic disease, in pregnancy and in cancer patients with fewer side effects than oral iron alone. High exposure to iron is associated with increased inflammation which is associated with worse cardiovascular outcomes. Lactoferrin can help reduce the total iron dose and hepatic inflammation.

Lactoferrin is a highly conserved, monomeric 80 kDa single polypeptide chain contained in most mammalian exocrine secretions, such as milk, saliva and tears, bronchial, and intestinal secretions. LTF is also found in the secondary granules of neutrophils a glycoprotein present in milk, has been demonstrated to possess a multitude of biological functions. Lactoferrin in Inflammation and Sepsis The antimicrobial activity of LTF is well documented and consists of two mechanisms: one is iron dependent and deals with high affinity of LTF to iron (bacteriostatic), and the other one is due to LTF affinity to lipopolysaccharide (LPS) to function as a direct bactericidal agent for Gram-negative organisms. Small changes, such as single nucleotide polymorphisms, can affect outcomes against pathogenic agents . LTF interacts with cell surface receptors involved in "danger signal" recognition \[e.g., toll-like receptor (TLR)4, CD14, and CD22\]. At the molecular level, LTF seems to reduce LPS-induced monocyte activation and subsequent production of pro-inflammatory mediators. Lactoferrin in Anemia in Liver Disease The hepatic expression of the hepcidin gene is regulated by signals which reflect body iron status and erythropoietic activity. The regulation of hepcidin by iron status includes a signal from the circulating transferrin via hepatocellular transferrin receptor (TfR2). Like transferrin, lactoferrin will deliver iron to hepatocytes but unlike transferrin, lactoferrin cannot deliver iron to erythroid cells. Lactoferrin does not interact with TfR1 or TfR2.