title: Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice.
abstract: Mice injected with endotoxin develop endotoxaemia and endotoxin-induced death, accompanied by the oxidative burst and overproduction of inflammatory mediators. Lactoferrin, an iron binding protein, provides a natural feedback mechanism to control the development of such metabolic imbalance and protects against deleterious effects of endotoxin. We investigated the effects of intraperitoneal administration of human lactoferrin on lipopolysaccharide (LPS)-induced release of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), interleukin 10 (IL-10) and nitric oxide (NO) in vivo. Lactoferrin was administered as a prophylactic, concurrent or therapeutic event relative to endotoxic shock by intravenous injection of LPS. Inflammatory mediators were measured in serum at 2, 6 and 18 h post-shock induction. Administration of lactoferrin 1 h before LPS resulted in a rather uniform inhibition of all mediators; TNF by 82%, IL-6 by 43%, IL-10 by 47% at 2 h following LPS injection,and reduction in NO (80%) at 6 h post-shock. Prophylactic administration of lactoferrin at 18 h prior to LPS injection resulted in similar decreases in TNF-alpha (95%) and in NO (62%), but no statistical reduction in IL-6 or IL-10. Similarly, when lactoferrin was administered as a therapeutic post-induction of endotoxic shock, significant reductions were apparent in TNF-alpha and NO in serum, but no significant effect was seen on IL-6 and IL-10. These results suggest that the mechanism of action for lactoferrin contains a component for differential regulation of cellular immune responses during in vivo models of sepsis.
authors.affiliation: University of Texas, Health Science Center at Houston, University of Houston, Houston, Texas 77030, USA. marian.l.kruzel@uth.tmc.edu
authors.forename: M L
authors.initials: ML
authors.lastname: Kruzel
authors.forename: Y
authors.initials: Y
authors.lastname: Harari
authors.forename: D
authors.initials: D
authors.lastname: Mailman
authors.forename: J K
authors.initials: JK
authors.lastname: Actor
authors.forename: M
authors.initials: M
authors.lastname: Zimecki
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy*; D005246:Feedback; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007781:Lactoferrin / Q000008:administration & dosage / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism; D016897:Respiratory Burst; D012772:Shock, Septic / Q000517:prevention & control*; D018746:Systemic Inflammatory Response Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D007781:Lactoferrin