Lactoferrin Scientific Studies

Orla M. Conneely, PhD

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas

Abstract

Lactoferrin is a non-heme iron binding glycoprotein produced during lactation and by epithelial cells at mucosal surfaces. The protein is a prominent component of the first line of mammalian host defense and its expression is upregulated in response to inflammatory stimuli. In this paper, the antibacterial and immune modulatory properties of lactoferrin that contribute to host defense are reviewed. In addition, the results of recent preclinical and clinical studies demonstrating that lactoferrin acts as an inhibitor of dermal inflammatory cytokine production are summarized. The results indicate that lactoferrin may act as a potent anti-inflammatory protein at local sites of inflammation including the respiratory and gastrointestinal tracts.

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Ann M. Mulder^a, Paul A. Connellan^a, Christopher J. Oliver^b, Carol A. Morris^a  , Lesley M. Stevenson<sup>a

a</sup> Center for Phytochemistry and Pharmacology, Southern Cross University, Lismore, NSW 2480, Australia

^b Blackmores Research Office, Southern Cross University, Lismore, NSW 2480, Australia

 Abstract

Dietary supplements of bovine lactoferrin are purported in consumer literature to enhance and support the immune system response through their antioxidant, antibacterial, and antiviral properties. Our aim was to investigate more fully the potential immune modulating properties and antioxidant activity of an oral supplementation of bovine lactoferrin in humans. Using an intraindividual repeated measure design, 8 healthy males aged 30 to 55 years, self-administered daily for 21 days, one capsule of placebo for 7 days, followed by 100 mg of lactoferrin for 7 days, followed by 200 mg of lactoferrin for 7 days. Peripheral blood lymphocyte subset counts, T-cell activation, natural killer (NK) cell cytotoxicity, serum cytokine levels (tumor necrosis factor [TNF]-α, interferon [IFN]-γ, interleukin [IL]-2, IL-4, IL-6, and IL-10), and serum hydrophilic, lipophilic, and total antioxidant capacity were repeatedly measured before and after each progressive supplementation. Statistically significant increases were found between presupplementation levels and levels after 200 mg of supplementation in total T-cell activation (as measure by CD3+) (P < .001), helper T-cell activation (as measure by CD4+) (P < .001), cytotoxic T-cell activation (as measured by CD8+) (P < .001), and hydrophilic antioxidant capacity (P < .05). No significant changes were seen in the other parameters measured. These results support the proposal that oral supplements of bovine lactoferrin may be a useful adjunct toward modulation of immune activity, in particular T-cell activation and antioxidant status.

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Marian L. Kruzel¹, Jeffrey K. Actor², Istvan Boldogh³, Michael Zimecki<sup>4

1</sup> Department of Integrative Biology and Pharmacology, the University of Texas, Health Science Center at Houston, Texas, U.S.A.

² Department of Pathology and Laboratory Medicine, the University of Texas, Health Science Center at Houston, Texas, U.S.A.

³ Department of Immunology and Microbiology, the University of Texas, Medical Branch at Galveston, Texas, U.S.A.

⁴ Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland

Abstract

Lactoferrin, an iron-binding glycoprotein, can be regarded as a cell-secreted mediator that bridges innate and adaptive immune function by regulating target cell response. It is a major pleiotropic mediator that directly assists in the development of T-helper cell polarization. The aim of this minireview is to provide a summary of the most recent work presented at the Lactoferrin Minisymposium at the University of Texas, Health Science Center at Houston, Texas, USA, regarding role of lactoferrin in maintaining immune homeostasis. The data presented here lay emphasis on the significance of lactoferrin in the resolution or progression of the immune responses, thus giving lactoferrin bookend properties in controlling the initial reactions to infectious assault, trauma, and injury. These findings may be critically important in the development of therapeutically relevant protocols.

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Mamoru Tomita^a, Hiroyuki Wakabayashi^b, Kouichirou^b, Shin, Koji Yamauchi^b, Tomoko Yaeshima^b, Keiji Iwatsuki<sup>b

a</sup> Dairy Techno Inc., 2-3-9 Shiba, Minato-ku, Tokyo 105-0014, Japan

^b Food Science & Technology Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama, Kanagawa 228-8583, Japan

Abstract

Lactoferrin (LF) was identified as a milk protein in 1960. Large-scale manufacturing of bovine LF (bLF) was established more than 20 years ago. Using this commercially available material, research for bLF applications has advanced from basic studies to clinical studies, and bLF has been applied to commercial food products for the last 25 years. During this period, it was found that LF is digested by gastric pepsin to generate a multi-potent peptide,  lactoferricin. It was also demonstrated that oral administration of bLF augments host protection against infections via antimicrobial action and immunomodulation of the host. In addition, researchers have demonstrated that oral administration of bLF preventscancer development. In this review, we look back on 25 years of bLF research and development.

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