The
Immune Function
by Kim Schoenhals
The
immune system is an incredibly intricate arrangement that prevents infection and
disease by moderating malignant and foreign cells within the body. Many unwanted
cells are simply devoured by the body's scavenger cells, although particularly
stalwart adversaries take longer to destroy. While the immune system works to
fend off these would-be invaders, the human host takes ill--fever and inflammation
are some outward signs of the body's inner fight.
During advancing years,
times of high stress or inadequate nutrition, the body's immune cells can become
sluggish and less effective. When this happens, opportunistic invaders settle
down to stay, potentially leading to serious infections, pneumonia or cancer.
The immune system is composed of several organs and systems, as well
as various types of immune cells. Organs that constitute the immune system--called
lymphoid organs--include the spleen and thymus. Additional components of the immune
system are lymph nodes and bone marrow.
Within bone marrow, lymphocytes
(white blood cells) are born to function as immune cells. Neutrophils are the
main circulating white blood cells, which seek out invaders when they are summoned
into action by other immune cells. They secrete toxins that kill antigens (invading
proteins) and devour them.
The two major classes of lymphocytes are B-cells,
which mature in the bone marrow and reside in the lymph system, and T-cells, which
mature in the thymus and circulate throughout the body. B-cells are responsible
for producing antibodies (a.k.a. immunoglobulins), which are proteins designed
to recognize and mark a specific antigen, while T-cells are charged with destroying
antigens that are tagged with an antibody.
There are three types of
T-cells: cytotoxic T-cells, helper T-cells and suppressor T-cells. Cytotoxic T-cells
attach themselves to malignant or infected cells. They secrete interferons, which
stop viruses from reproducing. Helper T-cells--including TH1 and TH2--assist cytotoxic
T-cells by recognizing an attack on the body, at which point cytotoxic T-cells
are sent to fight the infection. Helper T-cells also help the body's B-cells produce
antibodies. Suppressor T-cells are responsible for regulating the body's immune
response to invasions; they stop cytotoxic T-cells from releasing cytokines (immuno-regulatory
substances) and stop the production of immunoglobulins.
Immunoglobulins
exist in five classes: IgA, IgE, IgG, IgM and IgD. IgA is responsible for holding
off invaders or pushing them out of the body, which is why it exists in tears,
milk, sweat and saliva. IgE is involved in allergic reactions and encourages mast
cells to release histamine, as well as triggering inflammatory response. IgG is
specialized to kill certain bacteria and viruses, and activates enzymes that digest
invaders. IgM circulates in the bloodstream to kill bacteria. Finally, IgD circulates
in the blood system, but not much is known on its particular function.
Additional immune cells are scavenger cells called phagocytes--which include granulocytes
and macrophages. These cells seek out and devour invading cells. Macrophages are
generally stationary and protect a specific area, although they are also known
to travel to a point of infection to assist in warding off an antigen. They release
pyrogen, a substance that signals the body to increase temperature to induce fever,
which is oftentimes useful for killing pathogens.
Another scavenger,
the natural killer (NK) cell, destroys invaders without seeking out B-cells' tags.
NK cells search for foreign cells and kill them by releasing toxic enzymes and
interferons.
Just as NK cells secrete interferons, other immune cells
secrete interleukins, another type of cytokine, or immuno-regulatory substance.
These substances, which include monokines (secreted by monocytes) and lymphokines
(secreted by lymphocytes), are responsible for regulating the body's immune response,
such as the magnitude of an inflammation.
Interleukins, which are secreted
by macrophages, monocytes and some T-cells, include more than 30 types. Interleukin-1
is produced by macrophages and is involved in inducing fever, which can kill or
slow down a virus or bacterium. Interleukin-2 assists helper T-cells in encouraging
cytotoxic T-cells to kill invaders. Interleukin-4 enhances the B-cells' ability
to make antibodies (IgG and IgE in particular), and it stimulates helper T-cells
and cytotoxic T-cells. Interleukin-6 is released by macrophages, monocytes and
some T-cells, and induces B-cells to produce antibodies.
Tumor necrosis
factor (TNF) is released by macrophages to induce fever. It can kill cancer cells
and promotes the production of lymphokines.
With all of these cells and processes
for fending off invading microbes, fungi, bacteria and viruses, the immune system
has its work cut out for it, and there are numerous outward factors that can disrupt
the body's process of fighting off infection. Immunity can be disturbed through
anxiety1 and depression,2 as well as malnutrition.3 According to data from the
Natural Marketing Institute's (NMI) Health and Wellness Trends Database--three
years of trended data including more than 2,000 household respondents--more than
half of immune sufferers are also managing or treating stress, lack of energy,
joint pain and stiffness, and sleeplessness.
Because malnutrition adversely
affects immune function, ensuring proper nutrition through the diet is essential
to protecting and maintaining the immune system. In addition to nutrient intake,
several botanical and nutritional substances work to enhance the various activities
that make up immune function.
Micronutrients
"Micronutrient
starvation is a silent foe--its harmful effects may not be felt for years, yet
it is the No. 1 cause of poor immune function and, therefore, disease," wrote
Robert Rountree, M.D., and Carol Colman in Immunotics (G.P. Putnam's Sons, 2000).
"Micronutrients include vitamins, minerals and important chemicals found
in plant foods (called phytochemicals). Some micronutrients are well known, such
as vitamin C and calcium, while others may be less familiar, such as carotenoids
and bioflavonoids. ... Numerous studies have documented that when blood levels
of key vitamins, minerals and phytochemicals drop below optimal levels, our immune
systems don't function properly."
Antioxidants, those nutrients
known for combating free radical damage, are suggested for improving and maintaining
a healthy immune system. According to a research review out of GlaxoSmithKline
Consumer Healthcare in Parsippany, N.J., antioxidant micronutrients have been
consistently found to enhance lymphocyte proliferation, especially in the elderly.4
Vitamin C, an antioxidant vitamin, exists in lymphocyte and macrophage
cells. Consumers seeking a boost in immune function often turn to vitamin C, according
to NMI data. While 45.4 percent of the general population takes a vitamin C supplement,
67.8 percent of immune sufferers take the vitamin.
Researchers from Complutense
University in Madrid, Spain, conducted an in vitro experiment that demonstrated
when vitamin C was added to lymphocytes and macrophages, both types of cell showed
an increase in the intracellular levels of vitamin C, which was found to be especially
useful under oxidative stress conditions.5
A human trial conducted by
researchers at Karl-Franzens University Graz in Austria indicated vitamin C supplementation
does not necessarily correct neutrophil dysfunction brought on by exercise. They
gave six athletes 2 g/d of vitamin C for one week prior to a competition and compared
their immune function to four athletes who took no supplements. All athletes suffered
a significant reduction in neutrophil ability, and no differences were noted between
the groups.6
Similar to vitamin C, vitamin E is also popular among immune
sufferers, according to NMI. While 45.7 percent of the general population supplements
with vitamin E, 50.8 percent of immune sufferers do.
Taken together, vitamins
E and C were found to be effective adjuvant therapy for enhancing neutrophil performance
in patients with systemic vasculitis (inflamed lymph nodes). Researchers from
Birmingham University in England found that by treating patients with vitamins
E and C, neutrophil generation of superoxide was reduced, suggesting antioxidants
are important for treating vasculitis.7
In vitro research with vitamin
E indicated that the nutrient stimulates NK cell function. Researchers at Aga
Khan University in Karachi, Pakistan, also conducted animal research with vitamin
E. They learned that mice supplemented with 100 mg/d of alpha-tocopherol developed
increased NK cell activity. And, tocotrienol showed a similar response at ten
times lower a dose.8
Vitamin E was also found to improve the immune
function in patients with colorectal cancer. Researchers from Karolinska Institutet
in Stockholm, Sweden, administered 750 mg/d of vitamin E to 12 patients for two
weeks, after which time subjects exhibited increased T-cell ratios and a 10-percent
increase in the number of T-cells producing interleukin-2, compared with blood
levels prior to treatment.9
Coenzyme Q10 (CoQ10) is another micronutrient
with antioxidant effects that has been indicated in enhancing immune function.
According to in vitro research out of the University of Ancona in Italy, exposing
human lymphocytes to ubiquinol-10 (the reduced form of CoQ10) or CoQ10 enhanced
DNA resistance toward hydrogen peroxide-induced oxidation.10
In vivo
research conducted by scientists at the University Hospital Sant'Orsola-Malpighi
in Bologna, Italy, indicated CoQ10 concentrations are positively associated with
NK cell cytotoxicity in women. Researchers also noted elderly subjects (aged 90
to 106 years) tend to have inadequate CoQ10 status--in 40 percent of women and
24 percent of men.11
Selenium, an antioxidant mineral, also has application
in the realm of immune function. According to the Bologna researchers, serum selenium
concentrations were associated with the presence of NK cells. In addition, researchers
at the University of Surrey in Guildford, England, noted selenium deficiency had
adverse effects on immune function, and supplementation with the mineral was associated
with enhanced immune response.12
Selenium deficiency may allow invading
viruses to mutate and remain for a longer period in the host. This effect was
demonstrated by researchers at the University of North Carolina in Chapel Hill
and colleagues. They compared mice that received a selenium-deficient diet with
non-deficient animals, all of which were exposed to the human influenza virus.
The deficient mice had more severe cases of the flu that lasted for a longer period
of time, characterized by lung inflammation, than the non-deficient mice.13
Selenium supplementation has been shown to influence immune response, and when
combined with vitamin E, selenium's effects are more powerful, according to researchers
from the University of Hong Kong. They demonstrated that vitamin E and selenium
have interactive effects as oxygen radical scavengers, thereby promoting human
lymphocyte response to antigens.14
Alpha-lipoic acid, a powerful antioxidant,
is a vitamin-like, sulfur-containing compound that may improve immune function.
Alpha-lipoic acid's effect on immunity may be due to its ability to promote the
secretion of interleukin-2, according to researchers from the University of Sydney.
Through in vitro research, they demonstrated alpha-lipoic acid preferentially
induced apoptosis (cell death) among leukaemic T-cells.15
Alpha-lipoic
acid is also able to recycle other antioxidants, including vitamins C and E, CoQ10
and glutathione, another sulfur-containing compound. Levels of glutathione determine
macrophage, phagocyte and lymphocyte activity. Researchers from Tokyo University
of Science studied NK cell activity in mouse splenocytes that were zapped with
low dose gamma rays. They found that adding glutathione to splenocytes enhanced
the total cellular glutathione content and NK cell activity in a dose-dependent
manner.16
In addition to the antioxidant micronutrients, there are many
vitamins and minerals that have been shown to improve immune function. Vitamin
D, for example, is known for stimulating macrophage activity. And, the B vitamins
are known to help the body metabolize food into energy and synthesize antibodies
for the immune system. Vitamin B6, for example, is required to create antibodies
and slow tumor growth. Additionally, deficiencies of several nutrients, including
vitamin A, zinc and iron, are known to exist in populations where infectious disease
is a major health concern.17
Vitamin A deficiency has been linked with
immunity issues during pregnancy, according to researchers at the Rowett Research
Institute in Scotland. Their animal research demonstrated that vitamin A deficiency
during pregnancy caused abnormal placental apoptosis because the mother's neutrophils
were deprived of TNF-alpha.18
Zinc is an essential trace element that
influences the growth and integrity of the immune system, according to a research
review out of Universite Paris V Hopital Necker. Zinc impacts key immune mediators,
including enzymes, thymic peptides and cytokines, explaining the importance of
zinc status on lymphocyte activity.19
Researchers at the University
of California, Berkeley, studied the effects of a zinc-restricted diet on eight
healthy men and determined changes in lymphocyte proliferation and interleukin-2
expression were possibly early markers of mild zinc deficiency.20
Unpublished
animal research out of North Carolina State University in Raleigh showed that
a zinc-methionine complex (as OptiZinc™, manufactured by Benicia, Calif.-based
InterHealth Nutraceuticals Inc.) was able to enhance mononuclear-phagocytic function,
which is important for disease resistance and increased cellular immunity.
Iron is another mineral that is necessary for optimal immune response. Although
iron is part of the antioxidant enzyme catalase, it is not generally considered
an antioxidant. In fact, an excess of intracellular iron can increase the production
of free radicals, according to researchers at the Karolinska Institute in Stockholm,
Sweden. They conducted in vitro research and discovered that excess iron levels
also decrease the efficacy of TNF-alpha in protecting against liver cell damage.21
While excess iron can cause damage, the mineral is necessary for optimal
immune function, as it is crucial for lymphocyte and interleukin-2 proliferation,
according to researchers from Louisiana State University in Baton Rouge. They
conducted in vitro research and found iron affects an early step of T-cell activation.22
Copper is an essential trace mineral that is a cofactor in various enzyme
systems and is required for the maintenance of immune function. According to researchers
at the University of Ulster in Coleraine, Ireland, various immunological markers
have the potential to highlight marginal copper status. Some of the markers that
may lend insight to copper status include neutrophil function, interleukin-2 production,
blastogenic response to mitogens and lymphocyte subset phenotyping.23
Researchers from Oklahoma State University, Stillwater, conducted a human study
to determine the effects of copper and chromium supplementation on immune function.
They divided 40 postmenopausal women with high cholesterol into four groups: 1)
200 mcg/d of chromium; 2) 3 mg/d of copper; 3) both copper and chromium at the
same levels; or 4) .394 g/d of lactose as control. After 12 weeks, researchers
noted a significant interactive effect of chromium and copper supplementation
on lymphocyte proliferation, which was stimulated by the researchers. Lymphocyte
proliferation was significantly lower when copper was added to the chromium group,
and lymphocyte proliferation was significantly lower in the copper supplementation
group compared to the chromium group. Researchers concluded copper blocks enhancement
of lymphocyte proliferation by chromium supplementation, and copper supplementation
had suppressive effects on immune function in this study population.24
Immune Sufferers Are Generally Less Well Than GP
©The Health
& Wellness Trends Database.
The Natural Marketing Institute, 2002
Carotenoids and Flavonoids
Carotenoids are fat-soluble
pigments derived from plants that exhibit antioxidant properties and have been
studied in the realm of immune function. According to researchers at the Institute
of Nutritional Physiology in Karlsruhe, Germany, consuming a carotenoid-rich diet
can moderate T-cell function. In addition, dietary carotenoid intake can influence
the secretion of cytokines from helper T-cells, just as low carotenoid intake
can suppress this function.25
Lutein, one of the more well-known carotenoids,
naturally occurs in corn and spinach, although it is derived from marigolds for
commercial use. Animal research out of Washington State University in Pullman
indicated dietary lutein stimulates both cell-mediated and humoral (non-cellular)
immune responses. Female dogs fed dietary lutein for 12 weeks exhibited increased
lymphocyte proliferation and production of IgG.26 A similar study conducted by
the same team with female cats indicated those cats fed dietary lutein for 12
weeks demonstrated an immunomodulatory response.27
Lycopene, a carotenoid
found in high concentrations in tomato and tomato-based products, is a powerful
antioxidant and may be able to protect immune cells from oxidative damage, according
to researchers at the University of Milan in Italy. They administered 25 g/d of
tomato puree (containing 7 mg of lycopene) to nine adult women and evaluated the
ability of lymphocytes to withstand oxidative damage. Results indicated intake
of tomato puree increased plasma and lymphocyte lycopene concentrations, and reduced
lymphocyte DNA damage by approximately 50 percent.28
Aside from its
antioxidant capacity in protecting immune cells, lycopene may not increase immune
cell function. A study conducted by researchers at University College in Cork,
Ireland, failed to associate supplementation with low levels of lycopene (13.3
mg/d) with beneficial effects on cell-mediated immunity. The researchers administered
either lycopene, beta-carotene (8.2 mg/d) or placebo to 58 elderly subjects. After
12 weeks, researchers did not find beneficial or detrimental effects on immune
function in any of the groups.29
On the other hand, beta-carotene, a
carotenoid precursor of vitamin A, has been found to increase NK cell activity.
Researchers at Aga Khan University conducted an in vitro study and determined
that cells treated with beta-carotene at doses ranging from .1 mcg/ml to 10 mcg/ml
showed a significant increase in tumorolytic function--the ability to inhibit
pre-malignant cells. However, in doses of 2 ng/ml to 200 ng/ml, cells exhibited
a decrease in tumorolytic effects.30
A placebo-controlled study of beta-carotene
out of the University of Maryland in College Park garnered similar discouraging
results. Short-term beta-carotene supplementation (30 mg/d for 28 days) during
early lactation did not enhance T-cell immune competence in healthy women, although
it was found to increase plasma concentrations of beta-carotene and alpha-carotene.31
Astaxanthin, a carotenoid derived from algae, is also thought to enhance
NK cell activity. Researchers at the Institute for Health Care Science in Osaka,
Japan, discovered that stress reduced NK cell presence and caused liver tissue
damage in mice. However, when the animals were given daily oral astaxanthin, it
markedly slowed liver tissue damage.32
Additional animal research conducted
at the University of Minnesota in Minneapolis demonstrated similar findings. Astaxanthin-fed
mice exhibited an increased resistance to tumor growth, as well as higher cytotoxic
T-cell and interferon-gamma activity, compared to control mice that received none.33
Flavonoids, or bioflavonoids, are similar to carotenoids in that they are
plant pigments, although they are water-soluble rather than fat-soluble. Flavonoid
compounds are included in a class of substances called polyphenols.
Proanthocyanidins--a class of flavonoids also known as leucocyanidins, procyanidolic
oligomers (PCOs) or oligomeric procyanidins (OPCs)--exert antioxidant properties
and are an active constituent of grape seed extract.
Grape seed extract
may enhance the growth and viability of the normal human gastric mucosal cells
and murine macrophage cells. And, its proanthocyanidins are known to have anti-inflammatory
properties by inhibiting the degradation of mast cells (which release histamine).
Grape seed extract also appears to induce gamma interferon, which is derived
from helper T-cells (TH1), according to researchers at the State University of
New York at Buffalo. They conducted in vitro research and discovered a grape seed
extract exerted significant anti-tumor and antiviral effects by inducing production
of gamma interferon.34
Another derivative from the grape, resveratrol
is a polyphenol purported for its heart-healthy properties. Research out of the
Institute of Experimental Medicine in Rome indicated resveratrol also moderates
several human immune cell functions. Cells exposed to resveratrol at low levels
were stimulated to produce interferon gamma, interleukin-2 and interleukin-4,
while high concentrations of resveratrol suppressed this effect.35
Similar
to grape seed extract, cranberries contain proanthocyanidins. Cranberries also
contain additional flavonoids--flavonols and anthocyanins. According to researchers
at the University of Wisconsin, Madison, the immunomodulatory effects of the flavonoids
derived from cranberries may be responsible for their use in preventing heart
disease. They hypothesized flavonoid intake could affect immune response to oxidized
low-density lipoprotein (LDL) and its uptake by endothelial macrophages.36
Bilberry also contains a flavonoid complex that exhibits antioxidant function.
Anthocyanidins, the active constituents of bilberry, are thought to prevent inflammation
and are mediators of the immune substances that initiate inflammation such as
histamine, protease, leukotrienes and prostaglandins. The Commission E--a German
committee charged by the federal health agency with reviewing the safety and efficacy
of phytomedicines--approved internal use of bilberry to treat mild inflammation
of the mucous membranes of the mouth and throat.
Another extract that
contains flavonoids is pine bark. Specifically, pine bark extract contains OPCs
and phenolic acids, and is touted for its antioxidant properties. Researchers
from the University of California, Berkeley, noted French maritime pine bark extract
(as Pycnogenol®, distributed in North America by Hillside, N.J.-based Natural
Health Sciences) has strong free radical-scavenging activity, which is fostered
significantly by its OPCs.37
The same Berkeley researchers conducted
a study of French maritime pine bark as it relates to immune function. They learned
that the extract increased TNF-alpha secretion in a concentration- and time-dependent
manner. Researchers also said the OPCs modulated immune response in macrophages.38
A pilot study conducted as a collaboration between the University of Bucharest
in Romania and the University of Munster in Germany indicated French maritime
pine bark (as Pycnogenol) has immunoregulatory effects and may be beneficial for
patients with the autoimmune disease lupus. Six patients given the extract in
addition to their regular therapy exhibited a significant increase in lymphocyte
lifetime compared to five patients who remained on traditional therapy alone.39
Similar to OPCs and anthocyanins, soy isoflavones are considered flavonoids
and exhibit antioxidant effects. Researchers at the Food Research Program in British
Columbia conducted a research review of flavonoid compounds and their effects
on the production of TNF-alpha. They learned that the soy isoflavone genistein
inhibited TNF-alpha production, while the isoflavone daidzein enhanced production.40
In a human trial, researchers at St. Michael's Hospital in Toronto treated
41 hypercholesterolemic men and postmenopausal women with one of three diets:
1) low-fat dairy; 2) high-isoflavone (50 g/d of soy protein with 73 mg/d of isoflavones);
or 3) low-isoflavone (52 g/d of soy protein and 10 mg/d of isoflavones). After
one month, the women demonstrated significantly higher interleukin-6 values after
the high-isoflavone diet compared to control values. Researchers concluded this
finding may indicate an estrogenic effect of soy isoflavones in enhancing immune
response and may explain the lower incidence of certain cancers through immune
surveillance in soy-eating parts of the world.41
Green and black tea
contain polyphenolic compounds that have antioxidant properties and have been
studied for their effects on immune function. Researchers at Case Western Reserve
University in Cleveland conducted animal research with (-)-epigallacatechin-3-gallate
(EGCG), a phenolic compound extracted from green tea, and discovered that topical
application protects against UVB-induced immunosuppression in mice. Researchers
found that EGCG, when applied to the skin before exposure to UVB light, reduced
the number of monocytes, macrophages and neutrophils that infiltrated skin inflammatory
lesions, which may be responsible for creating UVB-induced immunosuppression.42
The same researchers continued this line of study and learned that pretreatment
with EGCG decreased oxidative damage to the skin and prevented UVB-induced immunosuppression
and skin cancer incidence.43
Another study out of the Institute of Radiation
Medicine in Beijing, China, indicated a possible protective effect against cancer
with green tea supplementation. When mice induced with Lewis lung carcinoma were
treated with green tea, mixed tea or tea polyphenol, the tea components prohibited
immune dysfunction and protected against exposure to the carcinogen. In addition,
researchers noted improved immune function in all mice receiving green tea.44
Immune Suferers Turns to Vitamins, Mineral and Herbal Supplements
at a Higher Rate Than GP ©The Health & Wellness Trends Database.
The Natural Marketing Institute, 2002
Mushrooms
Several medicinal mushrooms and their derivatives have been studied for their
immune-enhancing properties. "Just how mushrooms help stimulate the body's
immune system is a matter of controversy," wrote Harry Preuss, M.D., and
Sensuke Konno, Ph.D., in Maitake Magic (Freedom Press, 2002). "Most experts
agree that a key to their immune-stimulating properties is their content of polysaccharides--beta-glucans--that
in experimental and clinical studies have shown potential for boosting immunity
and preventing cancer."
Maitake (Grifola frondosa) is a medicinal
mushroom purported for its ability to improve immune function. Specifically, the
mushroom's beta-glucans are thought to enhance macrophage function. "Beta-glucans
impact a type of non-specific or generalized immune enhancement by supporting
the most fundamental aspect of immune function--the primitive, yet all-powerful,
macrophage," Preuss and Konno wrote. "Indeed, beta-glucans appear to
be essential to optimal immune function for virtually all life forms. They are
especially helpful against viral infections."
Specifically, the
polysaccharides derived from Maitake are thought to improve a patient's fight
against HIV and AIDS by preventing HIV-infected helper T-cells from dying, according
to Preuss and Konno. In addition, the authors noted Maitake can help stabilize
T-cell counts in HIV and AIDS patients, as well as improve levels of interleukin-1
and -2.
Researchers at Kobe Pharmaceutical University found Maitake's
beta-1,6 glucan and beta-1,3 glucan taken in addition to chemotherapy enhanced
immune cell activity by 1.2 to 1.4 times compared to chemotherapy alone.45 Some
of the same researchers sought to find how Maitake inhibits tumor formation and
found Maitake promoted TNF-alpha production.46 In another study, they noted Maitake
established immune balance between TH1 and TH2 cells, thereby inducing cellular
immunity in patients with an abundance of TH2 cells due to cancer.47
Another medicinal mushroom studied for its immune-enhancing and anti-tumor powers
is Reishi (Ganoderma lucidum), which contains active polysaccharides and is purported
to act as an antioxidant. A group of researchers from Hiroshima University in
Japan conducted two animal studies and concluded from both that a water-soluble
extract from a cultured medium of Reishi may act as a preventive agent against
colon cancer.48 The second study involved mice that were induced to cancer and
then fed either a diet with 5 percent Reishi or none for 10 weeks. Researchers
noted a significant reduction in tumor size in the Reishi group compared to control.49
Shiitake (Lentinus edodes) is another medicinal mushroom that has been
studied in the realm of immune function because of its polysaccharide content.
Shiitake is touted for improving immune function by activating macrophages, promoting
the recognition of antigens, increasing interleukin-1 production, promoting the
growth of B-cells and increasing antibody production.
Researchers at
the National University of Singapore determined that an aqueous extract of Shiitake
decreased interleukin-1 production and apoptosis in human neutrophils and was
found to increase interleukin-1 production and apoptosis in another line of immune
cells.50
Another medicinal mushroom that is said to have immune-enhancing
properties is Agaricus blazei (Himematsutake), which is also thought to act as
an anticarcinogen. Mice were implanted with two tumors, one of which was injected
with an Agaricus blazei Murill extract. Researchers saw a regression in both the
injected and non-injected tumors, and cited an activation of macrophages and neutrophils,
as well as an increase in serum levels of immunosuppressive acidic protein.51
Researchers at Kobe University in Japan determined that orally administered
Agaricus blazei also has anticarcinogenic potential. They treated mice with either
a hot, water-soluble fraction from the mushroom or saline solution. Mice receiving
the polysaccharide mixture exhibited anti-tumor activity and increased activity
of cytotoxic T-cells.52
AHCC® (Active Hexose Correlated Compound),
a hybridization of several species of medicinal mushrooms, has also been studied
for its immune-enhancing properties and anticarcinogenic effects. (Editor's note:
Amino Up Chemical Co. in Sopporo, Japan, owns the trademark for AHCC; Purchase,
N.Y.-based Maypro Industries distributes the raw material.)
AHCC is
thought to protect against cancer through its immune-enhancing effects. Recent
research out of Kansai Medical University in Japan indicated AHCC improved the
life expectancy of patients who received the supplement after undergoing surgery
for liver cancer, perhaps due to increased NK cell function.53
Botanicals
and Plant-Derived Compounds
The plant world is rife with immune-boosting
botanicals and plant-derived compounds. Echinacea is one such botanical that has
been touted for its ability to improve a person's odds against beating the common
cold. Research surrounding this botanical indicates it improves immune function.
A study conducted at the University of Alberta in Canada indicated that rats given
an oral preparation of echinacea twice daily for four days exhibited macrophage
activity and an increase in TNF-alpha.54
A study out of Southwest College
in Arizona compared the immunostimulatory effects of two echinacea species--Echinacea
purpurea (E. purpurea) and Echinacea angustifolia (E. angustifolia)--with the
immune-enhancing properties of larch arabinogalactan, extracted from Larix occidentalis.
Researchers administered various combinations of the extracts to 48 volunteers
for four weeks. Results indicated E. purpurea plus E. angustifolia, as well as
both echinacea extracts plus the larch arabinogalactan extract, increased production
of complement properdin, which is an indicator of immune system stimulation.55
Contrary to these results, researchers at the University of Idaho in Moscow
found no evidence of immunostimulatory activity from echinacea. During initial
testing, researchers administered the herb to female rats and found no increase
in NK cell or T-cell activity.56
Spirulina, a blue-green algae, has
immune-enhancing properties for which it has been studied as a chemopreventive
agent. Researchers from the Osaka Medical Center for Cancer and Cardiovascular
Diseases in Japan administered a hot water extract of Spirulina platensis to subjects
and found it enhanced NK cell function.57 In addition, a research review conducted
by Calipatria, Calif.-based Earthrise Nutritionals Inc. indicated spirulina may
protect against certain forms of cancer because of its effect on the immune system,
as well as its ability to repair DNA and protect against free radical damage.58
The aloe plant may also offer an extract that is helpful for immune
function. Acemannan, a major carbohydrate fraction of Aloe vera gel, is known
for activating immune response, and for its antiviral and anti-tumor activities,
according to researchers from Chungbuk National University in South Korea. They
studied acemannan's effects on dendritic cells, which are important for the initiation
of primary immune response. Acemannan was able to promote the maturation process
of these cells in vitro.59
As acemannan is derived from aloe, phytosterols
and phytosterolins can be extracted from various plants. These compounds are suspected
to inhibit cancer development because of their immune-balancing properties, according
to a research review conducted by Patrick J. Bouic, Ph.D., head of immunology
at the University of Stellenbosch in Cape Town, South Africa. Specifically, phytosterols
and phytosterolins promote lymphocyte activity.60
According to Bouic's
research, a proprietary sterols/sterolins mixture (as Moducare™, manufactured
by Eugene, Ore.-based EPI Moducare) increased interferon-gamma, which improved
the "fighting power" of immune cells. This action is important in the
prevention of cancer, according to Bouic. "The sterols/sterolins increase
the release of cytokines from immune cells," he explained. "These same
cytokines are responsible for making sure that the immune system is maintained
in a balanced mode. ... The cytokines that activate the killer cells are responsible
for 'neutralizing' other cytokines that promote the functioning of the cells making
the antibodies."
Keeping the immune system balanced is important
for reducing the occurrence of allergies, autoimmune conditions and viral infections,
according to Bouic. "The sterols/sterolins merely provide a safety mechanism
by making sure that the right factors are secreted and therefore ensuring that
we are always balanced immunologically," he added.
Another plant-derived
immunostimulant comes from garlic, which is popular among consumers. According
to NMI, 15.4 percent of the general population takes garlic supplements while
25.5 percent of immune sufferers take them.
Researchers from West Virginia
University in Morgantown conducted a research review to determine the mechanism
of action behind garlic's ability to inhibit tumor growth, which they hypothesized
was most likely due to immune stimulation. In comparing garlic to bacillus Calmette--Guerin
(an approved immunotherapy for human bladder cancer), researchers noted numerous
similarities. Both are known to stimulate growth of lymphocytes and macrophages,
induce the infiltration of these cells into transplanted tumors, increase spleen
size, and stimulate the release of interleukin-2, TNF-alpha and interferon-gamma,
as well as enhance NK cell and cytotoxic T-cell activity.61
Animal research
out of Healthcare Research Institute in Hiroshima, Japan, indicated aged garlic
extract also enhances immune function. In a series of experiments, researchers
learned the extract decreased antigen-specific ear swelling, increased NK cell
activities of spleen cells and prevented a decrease in spleen weight. Researchers
concluded aged garlic extract may be a promising candidate as an immune modifier,
which maintains the homeostasis of immune function, although further studies are
warranted to determine for which conditions it is most beneficial.62
Miscellaneous
While
many compounds are isolated from plants and studied for their individual effects,
some are studied in their entirety. Flaxseed, for example, has been studied in
the realm of women's health--specifically for preventing osteoporosis--and is
thought to act on immune health. Flaxseed has many active constituents, including
alpha linoleic acid (ALA), plant lignans and antioxidants.
"Essential
fatty acids from fish and flax oil are potent immune enhancers, as well as powerful
anti-inflammatory agents," wrote Lorna R. Vanderhaeghe and Bouic in The Immune
System Cure (Kensington Publishing Corp., 1999). They also noted that the lignans
found in flaxseed are known for their anti-cancer effects, as well as anti-fungal,
anti-bacterial and antiviral properties.
A research review out of the
Sky Park Wellness Center in Irvine, Calif., indicated dietary supplementation
with flaxseed and flaxseed oil, as well as fish oil, could significantly reduce
cytokine production while at the same time increasing calcium absorption, bone
calcium and bone density in postmenopausal women. According to the review, the
rapid rate of postmenopausal bone loss is mediated by interleukin-1, interleukin-6
and TNF-alpha. "Possibilities may exist for the therapeutic use of the omega-3
fatty acids, as supplements or in the diet, to blunt the increase of the inflammatory
bone-resorbing cytokines produced in the early postmenopausal years, in order
to slow the rapid rate of postmenopausal bone loss," the review's authors
wrote.63
Another EFA, conjugated linoleic acid (CLA), is suspected to
have immune-stimulating effects, according to a presentation given at a National
Institutes of Health workshop in May 2002--Perspectives on Conjugated Linoleic
Acid: Current Status and Future Directions. A 13-week human trial demonstrated
supplementation with CLA (as Clarinol™, manufactured by Channahon, Ill.-based
Loders Croklaan) stimulated immune response in humans by increasing the presence
of virus-specific antibodies. Using the hepatitis B vaccination as an infection
model, 75 human subjects were divided into three treatment groups: one control
group and two CLA groups. The two CLA groups received two different ratios of
the naturally occurring isomers c9, t11 and t10, c12; one group at a ratio of
50-to-50 and the other group at a ratio of 80-to-20. Those who received CLA with
equal (50-to-50) concentrations of the active isomers performed significantly
better than those in the control group or the 80-to-20 experimental group. At
the conclusion of the study, the antibody level in those who received CLA with
c9, t11 and t10, c12 in a 50-to-50 ratio was twice as high as those who received
CLA with those isomers in an 80-to-20 ratio or no CLA at all.
Probiotics,
which are "friendly" bacteria that live in the human intestinal tract,
are most commonly associated with digestive health, although they are thought
to promote immune health as well. In particular, probiotic supplements may increase
NK cell activity.
Researchers at Massey University in New Zealand suggested
probiotic supplementation would be especially useful among the elderly, as the
aging process can lead to declined cellular immunity. During a three-stage dietary
supplement trial, 30 healthy elderly volunteers consumed low-fat milk for three
weeks before and after either a low- or typical-dose regimen with Bifidobacterium
lactis (B. lactis) HN019. During the probiotic regimen, subjects exhibited increases
in the proportions of total, helper and activated T-cells and NK cells.64 The
same group of researchers conducted a separate study on elderly volunteers and
learned that supplementation with Lactobacillus rhamnosus (L. rhamnosus) also
had a positive effect on lymphocyte activity.65
Similar results were
reported by researchers at the National University of Taiwan. They involved 52
healthy middle-aged and elderly volunteers, who received L. rhamnosus HN001. After
supplementation with the probiotic in low-fat milk and lactose-hydrolyzed low-fat
milk for three weeks, NK cell activity increased by 71 percent and 147 percent,
respectively.66
Oral administration of Lactobacillus casei Shirota can
also enhance immunity by stimulating NK cell activity and the production of helper
T-cells, which repress the production of IgE antibodies, according to researchers
at Yakult Central Institute for Microbiological Research in Tokyo.67
Naturally occurring antibodies are also being studied for their immunoregulatory
effects when taken as supplements. Because human immunoglobulin is unsuitable
for supplementation, purified bovine antibodies are commonly used in commercial
preparations.
Research conducted with natural bovine IgG in 1992 demonstrated
the antibody was able to neutralize common pathogens, including E. coli and Cryptosporidia.68
Animal research published this year indicated supplementation with bovine serum
may be able to improve immune function and fight off opportunistic infection by
bacteria. Calves that were immuno-compromised due to Cryptosporidium parvum infection
were treated orally with natural bovine immunoglobin (as ImmunoLin™, manufactured
by Ames, Iowa-based Proliant Inc.), which was found to enhance the animals' recovery
from infection.69
The immunoglobins found in bovine colostrum are known
for providing the calf that receives them with the mother's innate protection
against microbial infection, according to researchers at the Agricultural Research
Centre of Finland. In addition, immunizing cows with pathogens or their antigens
can increase colostrum's concentration of specific antibodies against pathogens,
such as rotavirus, Shigella flexneri, Escherichia coli, Clostridium difficile,
Streptococcus mutans, Cryptosporidium parvum and Helicobacter pylori.70 The same
researchers reviewed the characteristics of bovine antibodies and the complement
system for use in health-promoting functional foods. They concluded, "Cow's
colostrum and milk contain virtually all compounds of bovine cellular and humoral
immune defense, including antibodies and complement proteins. ... The main limitation
of milk antibodies in human use is that they are derived from a foreign species
and can thus be used only against oral and gastrointestinal pathogens or for topical
applications. In order to overcome this limitation, it may be possible in the
future to produce human antibodies and complement proteins in transgenic cows."71
The immune system, which consists of humoral and cellular elements,
must perform at optimal levels to prevent invading antigens from taking hold and
causing illness. Several extrinsic factors (i.e., stress, anxiety and depression)
can tax the immune system and allow opportunistic invaders to settle in and cause
illness. For these reasons, nutrition is imperative to maintaining a healthy immune
system, especially during times of extrinsic stress, in order to ensure health
and wellness. The solution may lie within the natural products industry; several
micronutrients are required for keeping the immune system working properly, and
numerous botanical and nutritional supplements can be used to boost both cellular
and humoral immunity.
Editor's notes: Some content for this story
provided by Intramedicine (www.intramedicine.com).