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Title
Effect of zinc supplementation on cell-mediated immunity and
lymphocyte
subsets in preschool children.
Author
Sazawal S; Jalla S; Mazumder S; Sinha A; Black RE; Bhan MK
Address
ICMR Advanced Center for Diarrheal Disease Research, All India
Institute of Medical Sciences, New Delhi.
Source
Indian Pediatr, 34(7):589-97 1997 Jul
Abstract
OBJECTIVE: In a zinc supplementation trial (with a significant
impact
on diarrheal morbidity), to evaluate effect of zinc supplementation
on
cellular immune status before and after 120 days of supplementation.
DESIGN: A double blind, randomized controlled trial with immune
assessment at baseline and after 120 days on supplement. SETTING:
Community based study in an urban slum population. SUBJECTS:
Randomly
selected children (zinc 38, control 48), had a Multitest CMI
skin test
at both times. In 66 children (zinc 22, control 34), proportions
of
CD3, CD4, CD8, CD16, CD20 cells and the CD/CD8 ratio were also
estimated using a whole blood lysis method and flowcytometry.
INTERVENTION: zinc gluconate to provide elemental zinc 10 mg
daily and
20 mg during diarrhea. MAIN OUTCOME RESULTS: Regarding CMI, the
percentage of anergic or hypoergic children (using induration
score)
decreased from 67% to 47% in the zinc group, while in the control
group
it remained unchanged (73% vs 71%) (p = 0.05). The percentage
of
children deteriorating between first and second tests was significantly
lower in the zinc group (13% vs 33%, p = 0.03). Regarding lymphocyte
subsets, the zinc group had a significantly higher rise in the
geometric means of CD3 (25%, p = 0.02), CD4 (64% p = 0.001),
and
CD4/CD8 ratio (73% p = 0.004) with no difference in CD8 and CD20.
The
rise in CD4 was significantly higher in the zinc as compared
to the
control group; the ratio of geometric means was 1.45 (95% CI,
1.03-2.01). CONCLUSION: zinc supplementation improves cellular
immune
status, which may have been one of the mechanisms for observed
impact
of zinc supplementation on diarrheal morbidity.
Title
The age-associated decline in immune function of healthy individuals
is
not related to changes in plasma concentrations of beta-carotene'
retinol' alpha-tocopherol or zinc.
Author
Gardner EM; Bernstein ED; Dorfman M; Abrutyn E; Murasko DM
Address
Department of Medicine' Allegheny University of the Health Sciences'
Philadelphia' PA 19129' USA.
Source
Mech Ageing Dev, 94(1-3):55-69 1997 Mar
Abstract
The decline in the lymphoproliferative response to mitogenic
stimuli
shows marked heterogeneity in elderly individuals. Adequate nutriture
is required for optimal immune function' yet nutritional status
may be
compromised in the elderly. To Address whether this variation
in the
proliferative response of elderly individuals is related to their
nutritional status' we studied 61 elderly (80.5 +/- 5.7 year-old)
and
27 young (27.3 +/- 3.8 year-old) individuals participating in
an
ongoing assessment of their immune response to influenza vaccine.
Ambulatory elderly individuals were recruited from five different
retirement communities and were in good health upon enrollment
in the
study. Thirty-three percent of young and 54% of elderly subJects
reported consuming micronutrient supplements daily during the
study.
Plasma and peripheral blood mononuclear cells (PBMC) were isolated
from
fasting individuals twice' 4-6 weeks apart. At both times'
proliferative responses to the mitogens phytohemagglutinin (PHA)'
concanavalin A (Con A)' and pokeweed mitogen (PWM) were significantly
lower (P < 0.004) in the elderly compared to the young. However'
at
both times' elderly participants had plasma concentrations of
beta-carotene' retinol' alpha-tocopherol and zinc that were either
significantly greater than' or equal to' those of young subJects.
No
significant correlations between plasma concentrations of
beta-carotene' retinol' alpha-tocopherol and zinc and level of
proliferative responses to each stimuli were observed in elderly
individuals at either time. Thus' the heterogeneity in the
proliferative response to mitogenic stimuli exhibited by a healthy
elderly population cannot be attributed to differences in these
nutritional parameters.
Title
Stimulation of human peripheral blood mononuclear cells by zinc
and
related cations.
Author
Wellinghausen N; Driessen C; Rink L
Address
Institute of Immunology and Transfusion Medicine' University
of L ubeck
School of Medicine' Germany.
Source
Cytokine, 8(10):767-71 1996 Oct
Abstract
zinc is an important trace element for immune function. Here'
we show
that zinc addition in a serum- and lipopolysaccharide-free cell
culture
system leads to significantly enhanced levels of interleukin
1 beta
(IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) and
to
expression of the corresponding mRNA in human peripheral blood
mononuclear cells (PBMC). Structurally related divalent cations
like
cobalt' nickel' and mercury also partially increase monokine
secretion
but to a much lower and thus insignificant extent. They fail
to induce
mRNA of TNF-alpha after 3 h of culture. Therefore' monokine induction
is a zinc-specific effect influenced by the physicochemical properties
of the ion. Confirmation of the unique significance of zinc for
immune
function provides a better understanding of the mechanisms of
specific
zinc-mediated immune modulation.
Title
Energy restriction and zinc deficiency impair the functions of
murine T
cells and antigen-presenting cells during gastrointestinal nematode
infection.
Author
Shi HN; Scott ME; Stevenson MM; Koski KG
Address
Institute of Parasitology, Macdonald Campus of McGill University,
Ste.
Anne de Bellevue, QC H9X 3V9, Canada.
Source
J Nutr, 128(1):20-7 1998 Jan
Abstract
This study examined whether the impaired immune responses in
zinc
deficient- and/or energy-restricted mice exposed to a challenge
infection of Heligmosomoides polygyrus might be associated with
reduced
numbers of spleen cells, altered proportions of spleen cell
subpopulations and/or altered function of the T cells or
antigen-presenting cells (APC). Female BALB/c mice were given
free
access to either a zinc-sufficient (60 mg zinc/kg diet, Zn+)
or a
zinc-deficient diet (0.75 mg zinc/kg diet, Zn-) or were pair-fed
(PF)
the zinc-sufficient diet. Significant differences in parasite
burdens
were observed. Worm numbers were lowest in Zn+ mice, intermediate
in
the PF mice and highest in the Zn- mice, showing that both zinc
deficiency and energy restriction reduced protective immunity
against
the gastrointestinal nematode H. polygyrus. Although the absolute
numbers of spleen cells were reduced in both Zn- and energy-restricted
(PF) mice, neither deficiency altered the phenotypic distribution
of
the subpopulations of positive marker cells in the spleen. In
vitro
functional assays using a 1:1 ratio of APC:T cells showed that
T-cell
proliferation in response to parasite antigen (Ag) was impaired
by a
dietary effect of zinc deficiency on T cells and of energy restriction
and zinc deficiency on APC function. Consequences of the nutritional
deficiencies on cytokine production in response to parasite antigen
were more complex: zinc deficiency reduced T-cell function
[interleukin-4 and interleukin-5 (IL-4 and IL-5) production ,
and both
nutritional deficits depressed APC functions [IL-4, IL-5, and
interferon-gamma (IFN-gamma) production and T-cell function (IFN-gamma
production). Thus, this study showed that zinc deficiency and
energy
restriction played identifiably distinct roles in regulating
host
immune responses against the gastrointestinal nematode H. polygyrus.
Title
zinc metabolism in the brain: relevance to human neurodegenerative
disorders.
Author
Cuajungco MP; Lees GJ
Address
Department of Psychiatry and Behavioural Science, University
of
Auckland School of Medicine, New Zealand.
Source
Neurobiol Dis, 4(3-4):137-69 1997
Abstract
zinc is an important trace element in biology. An important pool
of
zinc in the brain is the one present in synaptic vesicles in
a subgroup
of glutamatergic neurons. In this form it can be released by
electrical
stimulation and may serve to modulate responses at receptors
for a
number of different neurotransmitters. These include both excitatory
and inhibitory receptors, particularly the NMDA and GABA(A) receptors.
This pool of zinc is the only form of zinc readily stained
histochemically (the chelatable zinc pool), but constitutes only
about
8% of the total zinc content in the brain. The remainder of the
zinc is
more or less tightly bound to proteins where it acts either as
a
component of the catalytic site of enzymes or in a structural
capacity.
The metabolism of zinc in the brain is regulated by a number
of
transport proteins, some of which have been recently characterized
by
gene cloning techniques. The intracellular concentration may
be
mediated both by efflux from the cell by the zinc transporter
ZrT1 and
by complexing with apothionein to form metallothlonein. Metallothionein
may serve as the Source of zinc for incorporation into proteins,
including a number of DNA transcription factors. However, zinc
is
readily released from metallothionein by disulfides, increasing
concentrations of which are formed under oxidative stress.
Metallothionein is a very good scavenger of free radicals, and
zinc
itself can also reduce oxidative stress by binding to thiol groups,
decreasing their oxidation. zinc is also a very potent inhibitor
of
nitric oxide synthase. Increased levels of chelatable zinc have
been
shown to be present in cell cultures of immune cells undergoing
apoptosis. This is very reminiscent of the zinc staining of neuronal
perikarya dying after an episode of ischemia or seizure activity.
Thus
a possible role of zinc in causing neuronal death in the brain
needs to
be fully investigated. intraventricular injections of calcium
EDTA have
already been shown to reduce neuronal death after a period of
ischemia.
Pharmacological doses of zinc cause neuronal death, and some
estimates
indicate that extracellular concentrations of zinc could reach
neurotoxic levels under pathological conditions. zinc is released
in
high concentrations from the hippocampus during seizures.
Unfortunately, there are contrasting observations as to whether
this
zinc serves to potentiate or decrease seizure activity. zinc
may have
an additional role in causing death in at least some neurons
damaged by
seizure activity and be involved in the sprouting phenomenon
which may
give rise to recurrent seizure propagation in the hippocampus.
In
Alzheimer's disease, zinc has been shown to aggregate beta-amyloid,
a
form which is potentially neurotoxic. The zinc-dependent transcription
factors NF-kappa B and Sp1 bind to the promoter region of the
amyloid
precursor protein (APP) gene. zinc also inhibits enzymes which
degrade
APP to nonamyloidogenic peptides and which degrade the soluble
form of
beta-amyloid. The changes in zinc metabolism which occur during
oxidative stress may be important in neurological diseases where
oxidative stress is implicated, such as Alzheimer's disease,
Parkinson's disease, and amyotrophic lateral sclerosis (ALS).
zinc is a
structural component of superoxide dismutase 1, mutations in
which give
rise to one form of familiar ALS. After HIV infection, zinc deficiency
is found which may be secondary to immune-induced cytokine synthesis.
zinc is involved in the replication of the HIV virus at a number
of
sites. These observations should stimulate further research into
the
role of zinc in neuropathology.
Title
Nutrition and immunity in the elderly: modification of immune
responses
with nutritional treatments.
Author
Lesourd BM
Address
Laboratoire d`Immunologie du vieillissement' Facult]e de M]edecine
Piti]e-Salp]etri`ere' Paris' France.
Source
Am J Clin Nutr, 66(2):478S-484S 1997 Aug
Abstract
Nutrition has a strong influence on the immune system of the
elderly.
Aging induces dysregulation of the immune system' mainly as a
result of
changes in cell-mediated immunity. Aging is associated with changes
to
the equilibrium of peripheral T and B lymphocyte subsets' such
as
decreases in the ratios of mature to immature' naive to memory'
T
helper 1 subset (TH1) to TH2' and CD5- to CD5+ cells. As a consequence'
cell-mediated immune responses are weaker and neither cell-mediated
nor
humoral responses are as well adapted to the antigen stimulus.
Undernutrition' common in aged populations' also induces lower
immune
responses' particularly in cell-mediated immunity. Protein-energy
malnutrition is associated with decreased lymphocyte proliferation'
reduced cytokine release' and lower antibody response to vaccines.
Micronutrient deficits' namely of zinc' selenium' and vitamin
B-6' all
of which are prevalent in aged populations' have the same influence
on
immune responses. Because aging and malnutrition exert cumulative
influences on immune responses' many elderly people have poor
cell-mediated immune responses and are therefore at a high risk
of
infection. Nutritional therapy may improve immune responses of
elderly
patients with protein-energy malnutrition. Supplementation with
high
pharmacologic doses of a single nutrient (zinc or vitamin E)
may be
useful for improving immune responses of self-sufficient elderly
people
living at home. Therefore' nutritional deficiency must be treated
in
the elderly to reduce infectious risk and possibly slow the aging
process.
Title
Micronutrients and immune function: some recent developments.
Author
Thurnham DI
Address
Human Nutrition Research Group, School of Biomedical Sciences,
University of Ulster, Coleraine, UK. di.thurnham@ulst.ac.uk
Source
J Clin Pathol, 50(11):887-91 1997 Nov
Abstract
Micronutrient deficiencies probably have few direct effects on
the
functioning of immune cells. The main effect appears to be a
reduction
in cell mass that may indirectly affect immune cell function,
particularly where T helper cell numbers are reduced. Results
of many
human studies are contradictory. Some of this contradiction may
be
accounted for by the fact that disease may lower concentrations
of
micronutrients in plasma that may be misinterpreted as deficiency.
Low
plasma vitamin A concentrations however appear to impair immune
responsiveness and have deleterious effects on membrane integrity
and
mucosal function. zinc may have similar effects on gut integrity
and
appears to be particularly useful in the treatment of acute diarrhoea.
Low concentrations of other nutrients such as ascorbate and iron,
may
not necessarily impair immune function. Low plasma ascorbate
may assist
the removal of iron from plasma and low iron concentrations appear
to
increase the cytotoxicity of macrophages.
Title
Influence of age and health on immune functions and trace elements.
Author
Licastro F; Chiricolo M; Morini MC; Capri I; Davis LJ; Conte
R; Mancini
R; Melotti C; Parente R; Serra R; et al
Address
Department of Experimental Pathology' University of Bologna'
Italy.
Source
Gerontology, 41(4):235-41 1995
Abstract
Apparently healthy elderly donors were screened according to
a simple
protocol that included clinical examination and the determination
of
hematological and biochemical values. This screening was performed
to
detect subclinical alterations which might interfere with immune
responses and trace element status. The elderly were divided
into two
groups. The first group consisted of 22 (age 76 +/- 1 years)
positively
selected elderly (PSE)' i.e. healthy subJects with no hematological
and
laboratory alterations' the second one comprised 13 (age 75 +/-
1
years) negatively selected elderly (NSE). Data were then compared
with
those obtained from 40 (age 35 +/- 2 years) healthy young controls.
In
both groups of elderly donors' plasma zinc levels were normal'
while
plasma copper concentrations were increased. Intracellular values
of
zinc and copper in mono- and polymorphonuclear cells from both
groups
of elderly were within reference limits. After in vitro activation'
granulocyte chemiluminescence activity was impaired only in NSE.
A
decrement in the number of circulating CD3 lymphocytes and an
increase
in CD8d' CD57 cells were found in PSE' while NSE showed an increased
number of CD3'DR cells and CD8d' CD57' CD8b'CD57 and CD16'CD56
positive
cells. Our results indicate that only plasma copper levels were
affected by age' whereas subclinical alterations in hematological
or
biochemical values appear to impair immune responses in the elderly.
Title
Trace elements in head and neck cancer patients: zinc status
and
immunologic functions.
Author
Prasad AS; Kaplan J; Beck FW; Penny HS; Shamsa FH; Salwen WA;
Marks SC;
Mathog RH
Address
Department of Internal Medicine' Wayne State University School
of
Medicine' Detroit' MI' USA.
Source
Otolaryngol Head Neck Surg, 116(6 Pt 1):624-9 1997 Jun
Abstract
In this study we have assessed zinc status and zinc-dependent
cell-mediated immune functions (interleukin-2 production by mononuclear
cells' natural killer cell lytic activity' and interleukin-1
beta
production by mononuclear cells) in adult patients with squamous
cell
carcinoma of the upper aerodigestive tract at diagnosis and before
any
therapy was instituted. Inasmuch as significant interactions
between
zinc' copper' and iron exist' we also assayed the plasma copper
level'
serum iron level' and total iron-binding capacity in our patients.
We
recruited 30 cancer subJects and 21 control subJects. On the
basis of
cellular zinc criteria' we diagnosed a mild deficiency of zinc
in 53%
of cancer subJects. The plasma zinc level was not decreased in
our
subJects. A univariate analysis was applied by use of one-way
analysis
of variance comparing study variables among the three study groups
(controls and zinc-deficient and zinc-sufficient cancer patients)
and
Tukey`s multiple comparison test' and we showed that interleukin-2
production and natural killer lytic activity were decreased in
zinc-deficient cancer patients. Interleukin-1 beta production
(ELISA
assay) was increased in both zinc-deficient and zinc-sufficient
groups.
Plasma copper level was not different' but the iron utilization
was
decreased in both groups of cancer subJects. We conclude that
zinc
deficiency and zinc-dependent immunologic dysfunctions are present
in
more than half of the patients with head and neck cancer in the
Detroit
area.
Title
Nutrition and the immune system: a review of nutrient-nutrient
interactions.
Author
Kubena KS; McMurray DN
Address
Department of Animal Science and Faculty of Nutrition' Texas
A&M
University' College Station 77843' USA.
Source
J Am Diet Assoc, 96(11):1156-64; quiz 1165-6 1996 Nov
Abstract
Although research on the role of single nutrients in immune function
is
extensive' this is not the case for multiple nutrients and subsequent
nutrient-nutrient interactions. After presenting a brief overview
of
immune function' the authors consider reports that examine imbalance
of
more than one nutrient and interactive effects on immunocompetence.
Availability of one nutrient may impair or enhance the action
of
another in the immune system' as reported for nutrients such
as vitamin
E and selenium' vitamin E and vitamin A' zinc and copper' and
dietary
fatty acids and vitamin A. Nutrient-nutrient interactions may
negatively affect immune function. For example' excess calcium
interferes with leukocyte function by displacing magnesium ions'
thereby reducing cell adhesion. Because of consumer interest
in
supplementation to improve immune function' the potential for
harm
exists. Research is needed to improve knowledge in this area
so that
recommendations can be made with more confidence. |
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