Abstract
It has been reported previously that oral administration of lactoferrin (LF) provides some host-protective effects against infections, cancers, and inflammations. In this review, we focus on the effect of oral LF on various infectious diseases and discuss the mechanism as elucidated in animal models. In the case of infections occurring at sites other than the digestive canal, it is unclear whether oral LF is absorbed from the intestine and exerts its protective effect at the site of infection. In preterm human infants, neonatal pigs, and rats with colitis, it was reported that LF is detectable in various body fluids after oral administration. We could not detect the transport of oral bovine LF into the blood of adult rats without gastrointestinal illness using several techniques, suggesting that there is an extremely low level of transport of LF, if any. Orally administered LF may act at the oro-gastro-intestinal mucosa and aid the defense system against infections through a network of mucosal immunity and systemic immunity. Indeed, it is reported that oral LF increases the number of cells in the leukocyte subset and cytokine (IFN-γ and IL-18) production in the intestinal mucosa of mice. Regarding systemic immunity, we have observed an increase of leukocyte number, cytokine (IFN-γ, TNF-α, IL-12, and IL-18) production, and effector activity of macrophages in response to LF administration in several animal models. These enhanced immune responses may contribute to eradication of the pathogen, resolution of the symptoms, and maintenance of the homeostasis during infectious diseases.
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References
Bhimani RS, Vendrov Y, Furmanski P. 1999 Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice. J Appl Microbiol 86, 135-144.
Harada E, Itoh Y, Sitizyo K, Takeuchi T, Araki Y, Kitagawa H. 1999 Characteristic transport of lactoferrin from the intestinal lumen into the bile via the blood in piglets. Comp Biochem Phys A 124, 321-327.
Hutchens TW, Henry JF, Yip T-T. 1991a Structurally intact (78-kDa) forms of maternal lactoferrin purified from urine of preterm infants fed human milk: Identification of a trypsin-like proteolytic cleavage event in vivo that does not result in fragment dissociation. Proc Natl Acad Sci USA 88, 2994-2998.
Hutchens TW, Henry JF, Yip T-T, Hachey DL, Schanler RJ, Motil KJ, Garza C. 1991b Origin of intact lactoferrin and its DNA-binding fragments found in the urine of human milk-fed preterm infants. Evaluation by stable isotopic enrichment. Pediatr Res 29, 243-250.
Kuhara T, Iigo M, Itoh T, Ushida Y, Sekine K, Terada N, Okamura H, Tsuda H. 2000 Orally administered lactoferrin exerts an antimetastatic effect and enhances production of IL-18 in the intestinal epithelium. Nutr Cancer 38, 192-199.
Takakura N, Wakabayashi H, Ishibashi H, Teraguchi S, Tamura Y, Yamaguchi H, Abe S. 2003 Oral lactoferrin treatment of experimental oral candidiasis in mice. Antimicrob Agents Chemother 47, 2619-2623.
Tanaka K, Ikeda M, Nozaki A, Kato N, Tsuda H, Saito S, Sekihara H. 1999 Lactoferrin inhibits hepatitis C virus viremia in patients with chronic hepatitis C: A pilot study. Jpn J Cancer Res 90, 367-371.
Teraguchi S, Shin K, Ogata T, Kingaku M, Kaino A, Miyauchi H, Fukuwatari Y, Shimamura S. 1995 Orally administered bovine lactoferrin inhibits bacterial translocation in mice fed bovine milk. Appl Environ Microbiol 61, 4131-4134.
Togawa J, Nagase H, Tanaka K, Inamori M, Umezawa T, Nakajima A, Naito M, Sato S, Saito T, Sekihara H. 2002 Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. Am J Physiol Gastrointest Liver Physiol 283, G187-G195.
Tomita M, Wakabayashi H, Yamauchi K, Teraguchi S, Hayasawa H. 2002 Bovine lactoferrin and lactoferricin derived from milk: production and applications. Biochem Cell Biol 80, 109-112.
Wada T, Aiba Y, Shimizu K, Takagi T, Koga Y. 1999 The therapeutic effect of bovine lactoferrin in the host infected with Helicobacter pylori. Scand J Gastroenterol 34, 238-243.
Wakabayashi H, Takakura N, Teraguchi S, Tamura Y. 2003 Lactoferrin feeding augments peritoneal macrophage activities in mice intraperitoneally injected with inactivated Candida albicans. Microbiol Immunol 47, 37-43.
Wakabayashi H, Takakura N, Yamauchi K, Teraguchi S, Uchida K, Yamaguchi H, Tamura Y. 2002 Effect of lactoferrin feeding on the host antifungal response in guinea pigs infected or immunized with Trichophyton mentagrophytes. J Med Microbiol 51, 844-850.
Wakabayashi H, Uchida K, Yamauchi K, Teraguchi S, Hayasawa H, Yamaguchi H. 2000 Lactoferrin given in food facilitates dermatophytosis cure in guinea pig models. J Antimicrob Chemother 46, 595-601.
Wang W-P, Iigo M, Sato J, Sekine K, Adachi I, Tsuda H. 2000 Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin. Jpn J Cancer Res 91, 1022-1027.
Yamauchi K, Hiruma M, Yamazaki N, Wakabayashi H, Kuwata H, Teraguchi S, Hayasawa H, Suegara N, Yamaguchi H. 2000 Oral administration of bovine lactoferrin for treatment of tinea pedis. A placebo-controlled, double-blind study. Mycoses 43, 197-202.
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Teraguchi, S., Wakabayashi, H., Kuwata, H. et al. Protection against infections by oral lactoferrin: Evaluation in animal models. Biometals 17, 231–234 (2004). https://doi.org/10.1023/B:BIOM.0000027697.83706.32
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DOI: https://doi.org/10.1023/B:BIOM.0000027697.83706.32