Relief Coloferrin New Zealand pure bovine colostrum
with 10% added lactoferrin.
Why
use Lactoferrin?
LACTOFERRIN RESEARCH
What
is Lactoferrin and what are the benefits?
o
Lactoferrin is a glycoprotein that belongs to the iron
transporter or transferrin family. It was originally isolated
from bovine milk, where it is found as a minor protein
component of whey proteins . Lactoferrin contains 703
amino acids and has a molecular weight of 80 kilodaltons.
In addition to its presence in milk, it is also found
in exocrine secretions of mammals and is released from
neutrophil granules during inflammation.
o Lactoferrin is considered a multifunctional or multi-tasking
protein. It appears to play several biological roles.
Owing to its iron-binding properties, lactoferrin is thought
to play a role in iron uptake by the intestinal mucosa
of the suckling neonate. That is, it appears to be the
source of iron for breast-fed infants. It also appears
to have antibacterial, antiviral, antifungal, anti-inflammatory,
antioxidant and immunomodulatory activities.
o Three isoforms of lactoferrin have been isolated: lactoferrin-alpha,
lactoferrin-beta and lactoferrin-gamma. Lactoferrin-beta
and lactoferrin-gamma have rnase activity, whereas lactoferrin-alpha
does not. Receptors for lactoferrin are found in monocytes,
lymphocytes, neutrophils, intestinal tissue and on certain
bacteria. Lactoferrin is abbreviated LF and Lf. Bovine
lactoferrin is abbreviated BLF.
o Bovine lactoferrin, derived from whey proteins, is marketed
as a nutritional supplement. Supplemental lactoferrin
typically contains low amounts of iron.
INFLUENCE
OF LACTOFERRIN ON THE IMMUNE SYSTEM
Introduction
o Lactoferrin has been shown to stimulate the immune system
by modulating the activity of immune-system components
during the course of infection.(1) Several studies have
demonstrated the effect of oral administration of lactoferrin
on the immune system.(1,2,3) Although the mechanisms by
lactoferrin influences the immune system are mostly unknown,
a variety of effects at a cellular and molecular level
have been documented.
o
Influence of Lactoferrin on cells of the Immune System.
Lymphocytes
Lactoferrin
has been shown to both enhance and inhibit lymphocyte
proliferation.
o
Oral administration of lactoferrin in mice resulted in
an increase of immunoglobulin A and G in the intestinal
fluid as well as proliferation of lymphocyte-producing
cells.
o
In patients with chronic hepatitis C, oral administration
of lactoferrin may increase the percentage of T helper
cells (Th0 and Th1) in the peripheral blood.
o
Lactoferrin was shown to promote the preferential maturation
of CD4 CD8 T cells to the T helper CD4 linage.
o
Lactoferrin can upregulate the CD4 surface marker in the
human Jurkat lymphocyte cell line.
o
Oral administration of lactoferrin was shown to increase
the number of CD4+ T cells and CD8 + T cells in the peripheral
blood, small intestine and spleen of mice.
Phagocytes
o Receptors for lactoferrin have been found on monocytes
and macrophages and research suggests that lactoferrin
helps to control the activity of these cells. Lactoferrin
assits the phagocytic action of these cells by promoting
the production of free radicals within the phagosome.
The proposed mechanism involves lactoferrin providing
iron to an oxygen radical-generating system.
Neutrophils
Lactoferrin is a key component of neutrophil cells and
influences their function in the following ways:
o
Stimulation of phagocytic activity. Lactoferrin catalyses
the production of hydroxyl radicals by providing iron.
o
Lactoferrin binds to the surface of the neutrphil cell
and promotes cell-to-cell interactions by reducing the
charge on the cell surface. The result is enhanced recruitment
and adherence of neutrophils to tissures at the site of
injury.
o Human or bovine lactoferrin stimulates 1L - 18 release
from neutrophils.
The
lactoferrin in neutrophils also augments the antimicrobial
capacity of macrophages, which ingest lactoferrin rich
granulocytes as their source of lactoferrin.
Natural
killer cells
o
Lactoferrin has been shown to increase the cytotoxicity
of killer cells in vitro. The mode of action is not clear
but appears to be independent of iron saturation.
o
Oral administration of lactoferrin was shown to increase
the number of natural killer cells inh the peripheral
blood and small intestine of mice.
Myelopoiesis
o
Lactoferrin has both positive and negative effects on
myelopoiesis. Lactoferrin saturated with iron has been
shown to inhibit myelopoiesis. The proposed mechanism
involves suppression of interleukin-1 production, which
in turn reduces granulocyte-monocyte stimulating factor
( GM-CSF) production.
Influence of lactoferrin on regulatory
components of the immune system.
Cytokines
o
Lactoferrin has been shown to regulate the production
and release of various cytokines such as interleukin-1
(IL-1), IL-2 and tumor necrosis factor ( TNF )-a and to
enhance the production of IL18 (INF-y inducing factor).
o
Oral administration of lactoferrin induces IL - 18 secretion
by epithelial cells of the small intestine in mice. Production
of interferon-y and IL-10 spleen cells were also increased
by lactoferrin feeding. These results suggest that oral
administration of lactoferrin has an inhibitory effect
on infection by modulating intestinal immunity.
Influence
of Lactoferrin on complement Activation
o Bovine lactoferrin was shown to bind to Streptococcus
agalactiae and activate the classical pathway of complement
by substituting for antibodies. The action of complement
increases the susceptibility of the bacteria to the action
of phgocytes ( a process known as opsonization ).
Influence
of Lactoferrin on complement Activation
o
The iron-building properties of lactoferrin serve to provide
an anti-oxidative effect of the immune system. By removing
iron, lactoferrin may inhabit the production of free radicals
and diminish oxidative damage to tissues. Lactoferrin
may also protect neutrophilic cells from lipid peroxidative
damage.
Mechanism
of immunomodulatory action of lactoferrin ( figure 1 page
111 Tomita. Bovine lactoferrin and lactoferricin derived
from milk: production and applications).
o Ingested lactoferrin is thought to act on intestinal
epithelial cells ( IEC ) and gut-associated lymphoid tissue
( GALT ) cells. Lactoferrin may interact with receptors
on the surfaces of these cells, causing the cells to produce
more IL-18 and other immunomodulatory factors. The factors
are then released into the bloodstream, where they may
stimulate white blood cells in the circulation.
Ability
of lactoferrin to suppress inflammation
o
LPS ( lipopolysaccharide ) is an endotoxin released from
Gram-negative bacteria upon their destruction. LPS is
a potent inflammatory mediator and can cause neutrophils
to increase their production and release of superoxide.
o Apo-lactoferrin can bind to LPS in the cell surface
of Gram-negative bacteria to prevent its powerful inflammatory
action. LPS is prevented from activating production of
such pro-inflammatory cytokines as tumour-necrosis factor
-x ( TNT-X ) IL-1 and IL-6.
o Research suggests that oral administration of bovine
lactoferrin in mice results in reduced inflammation, as
a result of the reduction in the pro-inflammatory cytokines
TNF -x, IL-1 IL-6, as well as with induction of the anti-inflammatory
cytokines IL-4 and IL-10.
Dosage and administration
o Oral lactoferrin dosed at 40mg daily has been used in
a couple of clinical trials of the substance. Those who
supplement with lactoferrin typically take 250 mg daily.
Lactoferrin is also found on colostrums and why protein
supplements.
Literature & references
1
Legrand, D. (2003) Lactoferrin and host defense: an overview
of its immuno-modulating and anti-inflammatory properties.
Sixth International Conference on Lactofferin: Structure,
Function and Applications - Capri, 5-9 May, 2003.
2
Artym, J.: M.: Paprocka, M. & Kruzel, M.L. (2003) Orally
administered lactoferrin restores humoral immune response
in immunocompromise mice. Immunlogy Letters 89(1): 9-15.
3
Kuhara, T: Ligo , T. Ushida, Y.:Sekine, K.; Terada, N.
Okamura, H. & Tsuda, H. (2001) Orally administered lactoferrin
exerts an antimetastatic effects and enhances production
of IL-18 in the intestinal epithelium. Nutrition and Cancer
38: 192-199.
Adamik B,Zimecki M, Wlasczyk A, et al. Lactoferrin effects
on the in vitro immune response in critically ill patients.Arch
Immunol Ther Exp (Warcz). 1998; 46:169-176
Baveye
S Elass E, Mazurier J, et al. Lactoferrin: a multifunctional
glycoprotein involved in the modulation of the inflammatory
process. Clin Chem Lab Med.1999; 1999; 37:281-286.
Britigan
BE, Serody JS, Cohen MS. The role of lactoferrin as an
anti-inflammatory molecule. Adv Exp Med Biol. 1994; 357:143-156.
Ikeda
M, Nozak A, Sugiyama K , et al. Characterization of antiviral
activity of lactoferrin against hepatitis C virus infection
in human cultured cells. Virus Res. 2000; 66:51-63.
Levay
PF, Viljoen M. Lactoferrin: a general review. Haemtologica.
1995; 80: 252-267.
Lonnerdal
B, Iyer S. Lactoferrin: molecular structure and biological
function. Annu Rev Nutr . 1995; 15:93-110.
Swart PJ, Kuipers EM, Smit C, et al. Lactoferrin. Antiviral
activity of lactoferrin. Adv Exp Med Biol. 1998; 443:205-213.
Trumpler
U, Straub PW, Rosenmund A. Antibacterial prophylaxis with
lactoferrin in neutropenic patients.Eur J Clin Microbiol
Infect Dis.1989; 8:310-313.
Vorland
LH. Lactoferrin: a multifunctional glycoprotein. APMIS.
1999; 107:971-981.
Vorland
LH.Ulvatne H, Andersen J, et al. Antibacterial effects
of lactoferrin B. Scand J Infect Dis.1999; 31:179-184.
Zimecki
M, Wlaszczyk A, Cheneau P, et al. Immunoregulatory effects
of a nutritional preparation containing bovine lactoferrin
taken orally by healthy individuals. Arch Immunol Ther
Exp (Warcz). 1998; 46:231-240.
More
Scientific and clinical studies to support lactoferrin
Strengthening
the immune barrier to help stop infection from getting
into the body 1.
Increasing
the number of immune cells to help keep you healthy and
to fight infection 2.
o Reference 1a) Debbabi, Dubarry, Rautureau et al 1998
Bovine Lactoferrin induces both mucosal and systemic immune
response in mice J Dairy Res . 65:283-293 , b) Miyauchi,
Kiano, Shinoda et al 1997 Immunoodulatory effect of Bovine
Lactoferrin Pepsin hydolysate on Murine Splenocytes and
Peyer's Patch cells J Dairy Sci 80:2330-2339
o Reference 2a) Ligo, Kuhara, Ushide et al 1999 inhibitory
effects of Bovine lactoferrin on colon carcinoma 26 lung
metastasis in mice Clin.Exp. Metastasis, 17:35-40 , b)
Wang, Lipo, Sato et al 2000 Activation of intestinal mucosal
immunity in tumour bearing mice by lactoferrin Jpn.J.Cancer
Res.91:1022-1027, c) Kuhara, Ligo, Ito et al orally administered
lactoferrin exerts an antimetastatic effect and enhances
production of II-18 in the intestinal epithelium.Nutr
Cancer, 38:192-199.
o
Lactoferrin (continued)
Searching
for a cure for the silent disease
Lactoferrin a milk protein offers hope of an Osteoporosis
cure.
Osteoporosis
is second only to cardiovascular disease in terms of global
health care problems, and currently affects 200 million
people and is predicted to increase steadily with the
growing numbers of elderly living longer, and obesity
adding extra strain on bones.
Reported
in Nutraingredients.com 25.11.04 Taking supplements of
lactofferin or a drink enriched with the milk protein
may help to prevent osteoporosis in those at risk, say
researchers from New Zealand, revealing for the first
time that the compound has powerful bone-building properties.
Auckland's
Osteoporosis Research Group has found that the milk protein,
produced commercially by Fonterra and Tatua , not only
inhibits bone breakdown but boosts bone growth four times
faster than normal when injected directly into bone cells.
Research leader Dr Jill Cornish unveiled the findings
at the World Dairy Summit in Melbourne Australia 25.11.04
It's
a goody molecule," Cornish said. " It is good for the
Immune system. It's anti-bacterial, anti-viral and anti-fungal.
When white blood cells respond to infection, they spurt
out lactoferrin naturally." The research is part of a
LactoPharma project a joint venture between Fonterra the
worlds largest diary ingredients producer and Auckland
UniServices Set up to discover and commercialise new bioactive
components in milk and colostrum.
Project leader Dr Cornish pointed out that a lot of research
has been done on the development of treatments to inhibit
bone resorption, but little is known about how to build
bone she added.
" This is what differentiates lactoferrin and makes it
so exciting-it's a double whammy if you like, inhibiting
the formation of cells that resorb bone and stimulating
the cells that form bone."
