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Zinc Trace Mineral

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Title
zinc and immune function.
Author
Ripa S; Ripa R
Address
Istituto di Clinica Medica Generale' Universit`a di Ferrara.
Source
Minerva Med, 86(7-8):315-8 1995 Jul-Aug
Abstract
zinc and immune function relationship has been extensively studied.
Both in experimentally induced mineral deficit and in genetically
determined deficit observable in acrodermatitis enteropathica and in
enteropathy of Danish A-46 cattle' a B and T dependent antibody
response decrease' a T dependent cytolytic response decrease and a
natural killer cytotoxic activity decrease are present noteviously.
Serious reduction of the immune function is present' in proportion to
the value of low zinc plasmatic level' in elderly patients' in
malnourished and seriously zinc deficient children' in patients
subJected to total parenteral supply' in HIV infections and especially
in evident AIDS: in this condition the plasmatic zinc level can be
considered' together with the CD4+ lymphocytes amount and the
B2-microglobulin value' a disease progression marker. zinc
immunostimulating action mechanisms are complex' although thymic
hormone (of which zinc is essential cofactor) stimulation seems to be
most important. zinc supplementation' also parenterally' can be useful
in immunodeficiency (in the elderly' in the post-surgical patients' in
genetically determined or alimentary induced deficit' in AIDS.

Title
The zinc pool is involved in the immune-reconstituting effect of
melatonin in pinealectomized mice.
Author
Mocchegiani E; Bulian D; Santarelli L; Tibaldi A; Muzzioli M; Lesnikov
V; Pierpaoli W; Fabris N
Address
Gerontol. Res. Dept.' Italian National Research Centres on Aging'
Ancona' Italy.
Source
J Pharmacol Exp Ther, 277(3):1200-8 1996 Jun
Abstract
Melatonin (MEL) affects the immune system by direct or indirect
mechanisms. An involvement of the zinc pool in the
immune-reconstituting effect of MEL in old mice has recently been
documented. An altered zinc turnover and impaired immune functions are
also evident in pinealectomized (px) mice. The present work
investigates further the effect of "physiological" doses of MEL on the
zinc pool and on thymic and peripheral immune functions in px mice.
Daily inJections of MEL (100 micrograms/mouse) for 1 month in px mice
restored the crude zinc balance from negative to positive values.
Thymic and peripheral immune functions' including plasma levels of
interleukin-2' also recovered. The nontoxic effect of MEL on immune
functions was observed in sham-operated mice. Because the half-life of
MEL is very short (12 min)' interruption of MEL treatment in px mice
resulted' after 1 month' in a renewed negative crude zinc balance and a
regression of immune functions. Both the zinc pool and immunological
parameters were restored by 30 further days of MEL treatment. The
existence of a significant correlation between zinc and thymic hormone
after both cycles of MEL treatment clearly shows an involvement of the
zinc pool in the immunoenhancing effects of MEL and thus suggests an
inter-relationship between zinc and MEL in px mice. Moreover' the
existence of significant positive correlations between zinc or thymulin
and interleukin-2 suggests that interleukin-2 may participate in the
action of MEL' via zinc' on thymic functions in px MEL-treated mice.

Title
Experimental studies on effects of zinc and germanium on immune
function and anti-oxidation in mice
Author
Xin H; Han T; Gong S
Address
General Hospital, Shenyang Command PLA.
Source
Chung Hua Yu Fang I Hsueh Tsa Chih, 30(4):221-4 1996 Jul
Abstract
zinc and germanium concentrations in serum, liver and muscle of mice,
T-lymphocyte subgroup proportion, serum superoxide dismutase (SOD)
activity and malonodialdehyde (MDA) were determined to study whether
there exist synergism or antagonism between zinc and germanium. Results
showed there existed, to certain extent, competitive effects of serum
zinc and germanium in mice. When concentration of serum zinc increased,
that of germanium decreased, or vise versa. There existed certain
relationship between zinc and germanium concentrations in serum and
those in muscle and liver of mice, and between those and CD3 count and
SOD activity. Immune function in mice was influenced and their
T-lymphocyte subgroup proportion changed with changes in serum zinc and
germanium concentrations. With increased germanium and decreased zinc
serum concentrations, CD3 and CD1 counts decreased, CD8 count
unchanged, and the ratio of CD1 to CD3 decreased, which showed certain
antagonist effects of them as they operated together. But, no
antagonism was observed in their anti-oxidant effects, SOD activity
increased to varied extent, and the level of MDA decreased.

Title
zinc and metallothioneins on cellular immune effectiveness during liver
regeneration in young and old mice.
Author
Mocchegiani E; Verbanac D; Santarelli L; Tibaldi A; Muzzioli M;
Radosevic-Stasic B; Milin C
Address
Immunology Ctr.' Res. Dept' Institute National Research Centers on
Aging' Ancona' Italy.
Source
Life Sci, 61(12):1125-45 1997
Abstract
Partial hepatectomy in young mice (pHx) induces thymic atrophy'
disregulation of thymocytes subsets and a strong accumulation of zinc
in thymic tissue after 1-2 days of liver regeneration. zinc is relevant
for good immune functioning. Restoration of zinc into both the thymus
and thymocytes subsets in the late period of liver regeneration is
observed in young pHx mice. These findings have suggested a link
between the thymus and the liver influencing T-cell functions and
involving zinc. This kind of link could be relevant in aging because
thymic involution' negative crude zinc balance and crippled immune
functions are constant events. The preminence of a liver extrathymic
T-cell pathway after pHx or during aging has been suggested. Thus the
study of pHx in young and old mice may offer a good model to better
understand the role played both by thymic involution and by liver
extrathymic T-cell pathway and the role of zinc in these physiological
processes during aging. Young pHx mice after 1-2 days of liver
regeneration show: reduced thymic endocrine activity' increment of
double negative (DN) thymocytes subsets' impairment of peripheral
immune efficiency (PHA' NK activity and IL-2) and negative crude zinc
balance' which are all restored in the late period of liver
regeneration. By contrast the thymic and peripheral immune defects and
the negative crude zinc balance' already present in old sham mice' are
not modified during liver regeneration in old pHx mice. Circulating
leukocytes and lymphocytes are not significantly modified both in young
and old pHx mice as compared to respective sham controls. zinc may also
be crucial for extrathymic T-cells pathway' being preminent in aging'
rather than in young age' due to its metallothioneins (MT) binding
capacity. MT are significantly increased in young pHx and in aging
inducing a low zinc-free quota for thymic and peripheral immune
efficiency in young pHx mice' and for extrathymic T-cell pathway' in
old age. Thus low zinc bioavailability' due to MT' may play a pivotal
role' not only for thymocytes but also for liver extrathymic T-cell
pathway.

Title
Role of the low zinc bioavailability on cellular immune effectiveness
in cystic fibrosis.
Author
Mocchegiani E; Provinciali M; Di Stefano G; Nobilini A; Caramia G;
Santarelli L; Tibaldi A; Fabris N
Address
Gerontology Research Department' Italian National Research Centers on
Aging (I.N.R.C.A.)' Ancona.
Source
Clin Immunol Immunopathol, 75(3):214-24 1995 Jun
Abstract
An altered cellular immune response as a secondary phenomenon has been
suggested to be probably involved in the bronchopulmonary infections by
Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty to
eradicate with modern anti-pseudomonal antibiotics the bronchopulmonary
infections has led us to further investigate the possible existence of
other cellular immune defects and their cause. Alterations in zinc
turnover are present in CF. zinc is relevant for good immune
functioning. In particular' zinc is required to confer biological
activity to thymulin (ZnFTS)' a biochemically defined thymic hormone
with a modulating action on cell-mediated immunity. The zinc-unbound
form (FTS) is inactive and it can be unmasked by in vitro zinc addition
to the plasma samples revealing the total amount of circulating
thymulin (active + inactive). Marginal zinc deficiencies may prevent
peripheral biological activation of active thymulin. Total
zinc-saturable thymulin fractions in CF are similar to those observed
in normal subJects' whereas the active quota is strongly reduced
associated with concomitant high plasma levels of inactive thymulin
compared to the values of healthy children (P < 0.01). A strict
correlation exists between zinc and thymic hormone-saturable fraction
(r = 0.87' P < 0.01) in CF. These findings suggest that the defect is
not due to a thymic failure but to a reduced peripheral saturation of
thymulin by zinc ions. This defect might depend on augmented plasma
concentration of alpha 2-macroglobulin' which has a higher binding
affinity for zinc than thymulin. T cell subsets are normal in CF.
Reduced NK cell number and activity are present. Also' plasma IL-2
levels are reduced. The existence of positive correlations between zinc
and IL-2 (r = 0.79' P < 0.01) and between zinc or active thymulin and
NK activity (r = 0.70' P < 0.01 and r = 0.88' P < 0.01' respectively)
suggest a close link among zinc failure' impaired IL-2 activity' low
thymulin level' and reduced NK activity in CF patients with both normal
and growth retardation. Although the role of NK cells is unknown in CF'
a zinc supplementation' in order to induce a complete saturation of
thymulin molecules' to correct some cellular immune defects and to
improve the growth' may be suggested.

Title
The effect of zinc and vitamin A supplementation on immune response in
an older population.
Author
Fortes C; Forastiere F; Agabiti N; Fano V; Pacifici R; Virgili F; Piras
G; Guidi L; Bartoloni C; Tricerri A; Zuccaro P; Ebrahim S; Perucci CA
Address
National Institute of Health, Rome, Italy.
Source
J Am Geriatr Soc, 46(1):19-26 1998 Jan
Abstract
OBJECTIVE: To determine if either supplemental vitamin A, zinc, or both
increases cell-mediated immune response in an older population. DESIGN:
A double-blind, randomized, controlled trial of supplementation with
vitamin A and zinc. SETTING: Casa Di Riposo Roma III, a public home for
older people in Rome, Italy. SUBJECTS: The health and nutritional
status of 178 residents were evaluated. One hundred thirty-six
residents agreed to participate in the trial and were randomized into
four treatment groups, and 118 of these residents completed the trial.
INTERVENTION: The four treatments consisted of: (1) Vitamin A (800
micrograms retinol palmitate); (2) zinc (25 mg as zinc sulfate); (3)
Vitamin A and zinc (800 micrograms retinol palmitate and 25 mg as zinc
sulfate); (4) Placebo capsules containing starch. MAIN OUTCOME
MEASUREMENTS: Immune tests-counts of leucocytes, lymphocytes, T-cell
subsets, and lymphocyte proliferative response to mitogens-were
measured before and after supplementation. RESULTS: zinc increased the
number of CD4 + DR + T-cells (P = .016) and cytotoxic T-lymphocytes (P
= .005). Subjects treated with vitamin A experienced a reduction in the
number of CD3 + T-cells (P = .012) and CD4 + T-cells (P = .012).
CONCLUSIONS: These data indicate that zinc supplementation improved
cell-mediated immune response, whereas vitamin A had a deleterious
effect in this older population. Further research is needed to clarify
the clinical significance of these findings.

Title
Increased urinary zinc excretion in cancer patients is linked to immune
activation and renal tubular cell dysfunction.
Author
Melichar B; Mal]i r F; Jand]ik P; Mal]i rov]a E; V]avrov]a J;
Mergancov]a J; Vobo ril Z
Address
Second Department of Internal Medicine' Charles University Medical
School' Hradec Kr]alov]e' Czech Republic.
Source
Biometals, 8(3):205-8 1995 Jul
Abstract
Urinary zinc excretion is known to be increased in cancer patients' but
the pathogenesis of this phenomenon remains uncertain. Both skeletal
muscle catabolism and renal tubular cell dysfunction have been proposed
to explain this observation. We have investigated urinary zinc and
N-acetyl-beta-D-glucosaminidase (NAG)' an indicator of renal tubular
cell dysfunction' as well as serum neopterin' an index of systemic
immune activation' in 22 patients with cancer and seven controls. Both
serum neopterin and urinary zinc were significantly elevated in cancer
patients (15.8 +/- 12.7 versus 7.3 +/- 2.3 nmol l-1 and 1.77 +/- 0.80
versus 1.21 +/- 0.41 mmol mol-1 creatinine' P < 0.02 and P < 0.05'
respectively)' while NAG was similar in cancer patients and the
controls (13.58 +/- 13.80 versus 13.68 +/- 12.19 mu kat mol-1
creatinine). A significant correlation was observed between serum
neopterin and urine zinc (rs = 0.5119' P < 0.02)' serum neopterin and
urine NAG (rs = 0.6761' P < 0.002)' and urinary zinc and NAG (rs =
0.6348' P < 0.002). In conclusion' the present data indicate a link
between urinary zinc excretion and immune activation as well as renal
tubular cell dysfunction. In addition' renal tubular cell dysfunction
appears to be linked to immune activation.

Title
zinc deficiency and energy restriction modify immune responses in mice
during both primary and challenge infection with Heligmosomoides
polygyrus (Nematoda).
Author
Shi HN; Koski KG; Stevenson MM; Scott ME
Address
Institute of Parasitology' McGill University' Quebec' Canada.
Source
Parasite Immunol, 19(8):363-73 1997 Aug
Abstract
This study characterized the consequences of zinc-sufficient (Zn+' 60
mg zinc/kg diet' ad libitum)' zinc-deficient (Zn-075 mg zinc/kg diet'
ad libitum) and energy-restricted (ER' 60 mg zinc/kg diet which was
restricted to match food intake of Zn- mice) diets on the in vivo and
in vitro immune response of BALB/c mice during both primary and
challenge infection with Heligmosomoides polygyrus. In Zn+ mice' both
primary and challenge infection with H. polygyrus induced not only a
strong Th2 response (IgE' IgG1' eosinophilia' IL-4' IL-5' IL-10)' but
also elements of a TH1 response (IgG3' IFN-gamma). zinc deficiency
significantly depressed Th2-dependent antibody production during both
primary and challenge infection' and reduced mitogen and
antigen-induced T cell proliferation during the challenge infection.
Th2 cytokine production was reduced by zinc deficiency (IL-4)' energy
restriction (IL-5) and by zinc deficiency possibly in combination with
energy restriction (IL-10) during the primary infection whereas TH1
cytokine production (IFN-gamma) was depressed during the challenge
infection by zinc deficiency' possibly together with energy
restriction. Both zinc deficiency and energy restriction reduced
eosinophilia with the more profound effect being exerted by zinc
deficiency. Thus' both zinc deficiency and its concurrent energy
restriction modify immune responses in the mice during primary and
challenge infection with H. polygyrus.

Title
Lower serum zinc in maJor depression is a sensitive marker of treatment
resistance and of the immune/inflammatory response in that illness.
Author
Maes M; Vandoolaeghe E; Neels H; Demedts P; Wauters A; Meltzer HY;
Altamura C; Desnyder R
Address
Clinical Research Center Mental Health' University Department of
Psychiatry' Antwerp' Belgium.
Source
Biol Psychiatry, 42(5):349-58 1997 Sep 1
Abstract
The aims of the present study were to examine i) serum zinc (Zn) and
copper (Cu) in treatment resistant depression (TRD); ii) the effects of
subchronic antidepressant therapy on these trace elements; and iii) the
relationships between serum Zn and Cu and immune/inflammatory markers.
Serum Zn was significantly lower in TRD than in normal controls. There
was a significant inverse correlation between baseline serum Zn and
staging of depression based on severity of prior treatment resistance.
There were no significant effects of antidepressive treatment on serum
Zn' whereas serum Cu was significantly reduced. There were highly
significant correlations between serum Zn and the CD4+/CD8+ T-cell
ratio (negative)' and total serum protein' serum albumin' and
transferrin (all positive). The results suggest that lower serum Zn is
a marker of TRD and of the immune/inflammatory response in depression.
It is suggested that treatment resistance may bear a relationship with
the immune/inflammatory alterations in maJor depression.

Title
Behaviour of zinc in physical exercise: a special reference to immunity
and fatigue.
Author
Cordova A; Alvarez-Mon M
Address
Department of Physiology and Biochemistry' University School of
Physiotherapy' University of Valladolid' Soria' Spain.
Source
Neurosci Biobehav Rev, 19(3):439-45 1995 Fall
Abstract
The variations in plasma zinc levels is dependent which follows
intensivity of exercise. It is clear that there are short-term effects
of exercise on zinc metabolism. It has also been shown that a high
level of constant exercise can have long-term effects on zinc
metabolism. It has been reported that runners have lower plasma zinc
levels than controls. Long term endurance training has been shown to
significantly decrease resting serum zinc levels in both male and
female athletes compared to sedentary controls. Severe zinc deficiency
can affect muscle function. One consequence of low serum zinc levels
could be a reduction in muscle zinc concentrations. Since zinc is
required for the activity of several enzymes in energy metabolism it
could be predicted that low muscle zinc levels would result in a
reduction in endurance capacity. zinc may also be acting directly at
membrane level; changes in extracellular zinc levels have been reported
to influence twitch-tension relationship in muscle. Some investigators
have associated acute and exhaustive exercise with decreased immune
function. The mechanisms by which physical stress modulates immune
competence are complex' involving both immune and neuroendocrine
messengers. Muscular fatigue is of critical importance and as such it
has been the subJect matter of numerous investigators. Although many
factors have been identified' a clear cause remains elusive. Factors
discussed include: energy supply' the accumulation of metabolites'
eccentric work' immune dysfunctions' etc. Recently we have demonstrated
that daily high and maintained physical training over a prolonged
period of time (7 mo) provokes marked modifications in the immune
system of elite sportsmen accompanied by a psychological and
biochemical stress level.(Abstract TRUNCATED AT 250 WORDS)

 

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