zinc and immune function.
Ripa S; Ripa R
Istituto di Clinica Medica Generale' Universit`a di Ferrara.
Minerva Med, 86(7-8):315-8 1995 Jul-Aug
zinc and immune function relationship has been extensively studied.
Both in experimentally induced mineral deficit and in genetically
determined deficit observable in acrodermatitis enteropathica
enteropathy of Danish A-46 cattle' a B and T dependent antibody
response decrease' a T dependent cytolytic response decrease
natural killer cytotoxic activity decrease are present noteviously.
Serious reduction of the immune function is present' in proportion
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
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
most important. zinc supplementation' also parenterally' can
in immunodeficiency (in the elderly' in the post-surgical patients'
genetically determined or alimentary induced deficit' in AIDS.
The zinc pool is involved in the immune-reconstituting effect
melatonin in pinealectomized mice.
Mocchegiani E; Bulian D; Santarelli L; Tibaldi A; Muzzioli M;
V; Pierpaoli W; Fabris N
Gerontol. Res. Dept.' Italian National Research Centres on Aging'
J Pharmacol Exp Ther, 277(3):1200-8 1996 Jun
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
documented. An altered zinc turnover and impaired immune functions
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
Daily inJections of MEL (100 micrograms/mouse) for 1 month in
restored the crude zinc balance from negative to positive values.
Thymic and peripheral immune functions' including plasma levels
interleukin-2' also recovered. The nontoxic effect of MEL on
functions was observed in sham-operated mice. Because the half-life
MEL is very short (12 min)' interruption of MEL treatment in
resulted' after 1 month' in a renewed negative crude zinc balance
regression of immune functions. Both the zinc pool and immunological
parameters were restored by 30 further days of MEL treatment.
existence of a significant correlation between zinc and thymic
after both cycles of MEL treatment clearly shows an involvement
zinc pool in the immunoenhancing effects of MEL and thus suggests
inter-relationship between zinc and MEL in px mice. Moreover'
existence of significant positive correlations between zinc or
and interleukin-2 suggests that interleukin-2 may participate
action of MEL' via zinc' on thymic functions in px MEL-treated
Experimental studies on effects of zinc and germanium on immune
function and anti-oxidation in mice
Xin H; Han T; Gong S
General Hospital, Shenyang Command PLA.
Chung Hua Yu Fang I Hsueh Tsa Chih, 30(4):221-4 1996 Jul
zinc and germanium concentrations in serum, liver and muscle
T-lymphocyte subgroup proportion, serum superoxide dismutase
activity and malonodialdehyde (MDA) were determined to study
there exist synergism or antagonism between zinc and germanium.
showed there existed, to certain extent, competitive effects
zinc and germanium in mice. When concentration of serum zinc
that of germanium decreased, or vise versa. There existed certain
relationship between zinc and germanium concentrations in serum
those in muscle and liver of mice, and between those and CD3
SOD activity. Immune function in mice was influenced and their
T-lymphocyte subgroup proportion changed with changes in serum
germanium concentrations. With increased germanium and decreased
serum concentrations, CD3 and CD1 counts decreased, CD8 count
unchanged, and the ratio of CD1 to CD3 decreased, which showed
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.
zinc and metallothioneins on cellular immune effectiveness during
regeneration in young and old mice.
Mocchegiani E; Verbanac D; Santarelli L; Tibaldi A; Muzzioli
Radosevic-Stasic B; Milin C
Immunology Ctr.' Res. Dept' Institute National Research Centers
Aging' Ancona' Italy.
Life Sci, 61(12):1125-45 1997
Partial hepatectomy in young mice (pHx) induces thymic atrophy'
disregulation of thymocytes subsets and a strong accumulation
in thymic tissue after 1-2 days of liver regeneration. zinc is
for good immune functioning. Restoration of zinc into both the
and thymocytes subsets in the late period of liver regeneration
observed in young pHx mice. These findings have suggested a link
between the thymus and the liver influencing T-cell functions
involving zinc. This kind of link could be relevant in aging
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.
study of pHx in young and old mice may offer a good model to
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
double negative (DN) thymocytes subsets' impairment of peripheral
immune efficiency (PHA' NK activity and IL-2) and negative crude
balance' which are all restored in the late period of liver
regeneration. By contrast the thymic and peripheral immune defects
the negative crude zinc balance' already present in old sham
not modified during liver regeneration in old pHx mice. Circulating
leukocytes and lymphocytes are not significantly modified both
and old pHx mice as compared to respective sham controls. zinc
be crucial for extrathymic T-cells pathway' being preminent in
rather than in young age' due to its metallothioneins (MT) binding
capacity. MT are significantly increased in young pHx and in
inducing a low zinc-free quota for thymic and peripheral immune
efficiency in young pHx mice' and for extrathymic T-cell pathway'
old age. Thus low zinc bioavailability' due to MT' may play a
role' not only for thymocytes but also for liver extrathymic
Role of the low zinc bioavailability on cellular immune effectiveness
in cystic fibrosis.
Mocchegiani E; Provinciali M; Di Stefano G; Nobilini A; Caramia
Santarelli L; Tibaldi A; Fabris N
Gerontology Research Department' Italian National Research Centers
Aging (I.N.R.C.A.)' Ancona.
Clin Immunol Immunopathol, 75(3):214-24 1995 Jun
An altered cellular immune response as a secondary phenomenon
suggested to be probably involved in the bronchopulmonary infections
Pseudomonas aeruginosa in cystic fibrosis (CF). The difficulty
eradicate with modern anti-pseudomonal antibiotics the bronchopulmonary
infections has led us to further investigate the possible existence
other cellular immune defects and their cause. Alterations in
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
with a modulating action on cell-mediated immunity. The zinc-unbound
form (FTS) is inactive and it can be unmasked by in vitro zinc
to the plasma samples revealing the total amount of circulating
thymulin (active + inactive). Marginal zinc deficiencies may
peripheral biological activation of active thymulin. Total
zinc-saturable thymulin fractions in CF are similar to those
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
(r = 0.87' P < 0.01) in CF. These findings suggest that the
not due to a thymic failure but to a reduced peripheral saturation
thymulin by zinc ions. This defect might depend on augmented
concentration of alpha 2-macroglobulin' which has a higher binding
affinity for zinc than thymulin. T cell subsets are normal in
Reduced NK cell number and activity are present. Also' plasma
levels are reduced. The existence of positive correlations between
and IL-2 (r = 0.79' P < 0.01) and between zinc or active thymulin
NK activity (r = 0.70' P < 0.01 and r = 0.88' P < 0.01'
suggest a close link among zinc failure' impaired IL-2 activity'
thymulin level' and reduced NK activity in CF patients with both
and growth retardation. Although the role of NK cells is unknown
a zinc supplementation' in order to induce a complete saturation
thymulin molecules' to correct some cellular immune defects and
improve the growth' may be suggested.
The effect of zinc and vitamin A supplementation on immune response
an older population.
Fortes C; Forastiere F; Agabiti N; Fano V; Pacifici R; Virgili
G; Guidi L; Bartoloni C; Tricerri A; Zuccaro P; Ebrahim S; Perucci
National Institute of Health, Rome, Italy.
J Am Geriatr Soc, 46(1):19-26 1998 Jan
OBJECTIVE: To determine if either supplemental vitamin A, zinc,
increases cell-mediated immune response in an older population.
A double-blind, randomized, controlled trial of supplementation
vitamin A and zinc. SETTING: Casa Di Riposo Roma III, a public
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
four treatment groups, and 118 of these residents completed the
INTERVENTION: The four treatments consisted of: (1) Vitamin A
micrograms retinol palmitate); (2) zinc (25 mg as zinc sulfate);
Vitamin A and zinc (800 micrograms retinol palmitate and 25 mg
sulfate); (4) Placebo capsules containing starch. MAIN OUTCOME
MEASUREMENTS: Immune tests-counts of leucocytes, lymphocytes,
subsets, and lymphocyte proliferative response to mitogens-were
measured before and after supplementation. RESULTS: zinc increased
number of CD4 + DR + T-cells (P = .016) and cytotoxic T-lymphocytes
= .005). Subjects treated with vitamin A experienced a reduction
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
the clinical significance of these findings.
Increased urinary zinc excretion in cancer patients is linked
activation and renal tubular cell dysfunction.
Melichar B; Mal]i r F; Jand]ik P; Mal]i rov]a E; V]avrov]a J;
Mergancov]a J; Vobo ril Z
Second Department of Internal Medicine' Charles University Medical
School' Hradec Kr]alov]e' Czech Republic.
Biometals, 8(3):205-8 1995 Jul
Urinary zinc excretion is known to be increased in cancer patients'
the pathogenesis of this phenomenon remains uncertain. Both skeletal
muscle catabolism and renal tubular cell dysfunction have been
to explain this observation. We have investigated urinary zinc
N-acetyl-beta-D-glucosaminidase (NAG)' an indicator of renal
cell dysfunction' as well as serum neopterin' an index of systemic
immune activation' in 22 patients with cancer and seven controls.
serum neopterin and urinary zinc were significantly elevated
patients (15.8 +/- 12.7 versus 7.3 +/- 2.3 nmol l-1 and 1.77
versus 1.21 +/- 0.41 mmol mol-1 creatinine' P < 0.02 and P
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
urine NAG (rs = 0.6761' P < 0.002)' and urinary zinc and NAG
0.6348' P < 0.002). In conclusion' the present data indicate
between urinary zinc excretion and immune activation as well
tubular cell dysfunction. In addition' renal tubular cell dysfunction
appears to be linked to immune activation.
zinc deficiency and energy restriction modify immune responses
during both primary and challenge infection with Heligmosomoides
Shi HN; Koski KG; Stevenson MM; Scott ME
Institute of Parasitology' McGill University' Quebec' Canada.
Parasite Immunol, 19(8):363-73 1997 Aug
This study characterized the consequences of zinc-sufficient
mg zinc/kg diet' ad libitum)' zinc-deficient (Zn-075 mg zinc/kg
ad libitum) and energy-restricted (ER' 60 mg zinc/kg diet which
restricted to match food intake of Zn- mice) diets on the in
in vitro immune response of BALB/c mice during both primary and
challenge infection with Heligmosomoides polygyrus. In Zn+ mice'
primary and challenge infection with H. polygyrus induced not
strong Th2 response (IgE' IgG1' eosinophilia' IL-4' IL-5' IL-10)'
also elements of a TH1 response (IgG3' IFN-gamma). zinc deficiency
significantly depressed Th2-dependent antibody production during
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)'
restriction (IL-5) and by zinc deficiency possibly in combination
energy restriction (IL-10) during the primary infection whereas
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
challenge infection with H. polygyrus.
Lower serum zinc in maJor depression is a sensitive marker of
resistance and of the immune/inflammatory response in that illness.
Maes M; Vandoolaeghe E; Neels H; Demedts P; Wauters A; Meltzer
Altamura C; Desnyder R
Clinical Research Center Mental Health' University Department
Psychiatry' Antwerp' Belgium.
Biol Psychiatry, 42(5):349-58 1997 Sep 1
The aims of the present study were to examine i) serum zinc (Zn)
copper (Cu) in treatment resistant depression (TRD); ii) the
subchronic antidepressant therapy on these trace elements; and
relationships between serum Zn and Cu and immune/inflammatory
Serum Zn was significantly lower in TRD than in normal controls.
was a significant inverse correlation between baseline serum
staging of depression based on severity of prior treatment resistance.
There were no significant effects of antidepressive treatment
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
a marker of TRD and of the immune/inflammatory response in depression.
It is suggested that treatment resistance may bear a relationship
the immune/inflammatory alterations in maJor depression.
Behaviour of zinc in physical exercise: a special reference to
Cordova A; Alvarez-Mon M
Department of Physiology and Biochemistry' University School
Physiotherapy' University of Valladolid' Soria' Spain.
Neurosci Biobehav Rev, 19(3):439-45 1995 Fall
The variations in plasma zinc levels is dependent which follows
intensivity of exercise. It is clear that there are short-term
of exercise on zinc metabolism. It has also been shown that a
level of constant exercise can have long-term effects on zinc
metabolism. It has been reported that runners have lower plasma
levels than controls. Long term endurance training has been shown
significantly decrease resting serum zinc levels in both male
female athletes compared to sedentary controls. Severe zinc deficiency
can affect muscle function. One consequence of low serum zinc
could be a reduction in muscle zinc concentrations. Since zinc
required for the activity of several enzymes in energy metabolism
could be predicted that low muscle zinc levels would result in
reduction in endurance capacity. zinc may also be acting directly
membrane level; changes in extracellular zinc levels have been
to influence twitch-tension relationship in muscle. Some investigators
have associated acute and exhaustive exercise with decreased
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
has been the subJect matter of numerous investigators. Although
factors have been identified' a clear cause remains elusive.
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)