title: Anti-inflammatory effects of orally ingested lactoferrin and glycine in different zymosan-induced inflammation models: evidence for synergistic activity.
abstract: There is a growing awareness of the interaction of food constituents with the immune system. The present study aims to evaluate the anti-inflammatory effects of two of these nutritional components (glycine and bovine-lactoferrin (b-LF)) using two different mouse models. In a zymosan-induced ear-skin inflammation model both components decreased the inflammatory response locally (ear swelling and inflammatory cytokine concentration in the ears) and systemically (number of TNF-alpha producing spleen cells). Glycine effects (20, 50 or 100 mg/mouse/day) were concentration dependent. B-LF (0.1 or 1 mg/mouse/day) inhibited the inflammatory response although higher doses (5 and 25 mg/mouse/day) were not effective. A combination of b-LF 0.1 mg/mouse/day and glycine 20 or 50 mg/mouse/day counteracted the zymosan-induced ear swelling synergistically and enhanced the decrease in the number of TNF-alpha producing spleen cells of the individual components. In a zymosan-induced acute arthritis model glycine (50 mg/mouse/day) inhibited joint swelling, inflammatory cell infiltration and cartilage proteoglycan depletion. A b-LF dose of 5 mg/mouse/day reduced the zymosan-induced joint swelling without modulating inflammatory cell infiltration and cartilage proteoglycan depletion. The present study indicates that the anti-inflammatory effects of glycine are independent of the used models. B-LF displays a reversed concentration dependency and the activity is model dependent. A combination of glycine and lactoferrin demonstrated a synergistic anti-inflammatory effect on zymosan-induced skin inflammation and an enhanced decrease in the number of TNF-alpha producing spleen cells compared to the effect of the single components. Therefore, this nutritional concept might be a new option for the treatment of chronic inflammatory diseases.
authors.affiliation: Numico Research, Wageningen, The Netherlands. anita.hartog@numico-research.nl
authors.forename: Anita
authors.initials: A
authors.lastname: Hartog
authors.forename: Inge
authors.initials: I
authors.lastname: Leenders
authors.forename: Peter M
authors.initials: PM
authors.lastname: van der Kraan
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011509:Proteoglycans / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015054:Zymosan
chemical_list: D000893:Anti-Inflammatory Agents; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D015054:Zymosan; D007781:Lactoferrin; D005998:Glycine