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Effects of selenium supplementation on immune parameters in chronic
uraemic patients on haemodialysis.
Bonomini M; Forster S; De Risio F; Rychly J; Nebe B; Manfrini V;
Klinkmann H; Albertazzi A
Institute of Nephrology' University of Chieti' Italy.
Nephrol Dial Transplant, 10(9):1654-61 1995
BACKGROUND. The involvement of selenium (Se) in immune response has
been increasingly recognized' cell-mediated immunity being principally
affected by Se deficiency. Blood Se levels in chronic uraemic patients
are frequently lower than in controls' and in these patients cellular
immunity in generally impaired. METHODS. The present study was designed
to assess the effects of Se supplementation over 6 consecutive months
on immune parameters in haemodialysis (HD) patients from Rostock
(Germany) and Chieti (Italy). In both cities' five patients were
supplemented with Se (500 micrograms thrice weekly for 3 months' then
200 micrograms thrice weekly for the next 3 months)' whereas another
five patients received placebo. All Se determinations were performed in
a single laboratory. RESULTS. In both cities' basic plasma Se levels
were significantly lower in patients than in their corresponding normal
controls. After beginning Se supplementation' plasma Se concentration
promptly normalized and levelled off in the normal range throughout the
study. Se administration was well tolerated by all patients' and no
side-effects attributable to Se toxicity were observed. Although no
maJor change in immunocompetent cells (white blood count' total
lymphocyte count' lymphocyte subpopulations) was observed during Se
therapy' an improvement in T-cell response to phytohaemoagglutinin (as
evaluated in Rostock patients) and a significant progressive increase
in delayed-type hypersensitivity (as evaluated in Chieti patients) was
observed in supplemented patients. After 6 months of Se therapy' the
increase in delayed-type hypersensitivity of supplemented patients
proved to be significantly higher when compared to both
presupplementation values and to the results found in non-supplemented
patients. Three months after suspension of Se supplementation' plasma
Se levels and delayed hypersensitivity significantly decreased in
Chieti patients' with both parameters returning similar to
presupplementation values. CONCLUSIONS. In accordance with previous
studies done in non-uraemic subJects' our investigation demonstrates
for the first time the immunostimulatory properties of Se in HD
patients. Though several problems on Se metabolism in uraemia remain
unresolved' in our opinion moderate and safe Se supplementation can be
beneficial in chronic uraemic patients.

Effects of selenium and vitamin E on the immune responses of domestic
Finch JM; Turner RJ
AFRC Institute for Animal Health' Compton Laboratory' Newbury.
Res Vet Sci, 60(2):97-106 1996 Mar
The gross effects of selenium and vitamin E deficiency on animal
production and the potential benefits of supplementation are
recognised' and the influence of these micronutrients on the resistance
of animals to a variety of infections has also been reported. As a
result' deficiencies could compromise the immune system and result in a
decline in production and performance before gross effects become
apparent. Data obtained by laboratories studying different animal
species indicate that the responses of domestic animals' particularly
ruminants' differ from those of human beings and laboratory animals as
well as differing among themselves. This paper provides a comprehensive
review of the effects of selenium and vitamin E on the immune responses
of domestic animals and discusses their effects with respect to the
differences in the basal nutritional status of the animals concerned'
the type of supplements used' the route and timing of their
administration and the different agents which have been used to
stimulate an immune response.

High risk of HIV-related mortality is associated with selenium
Baum MK; Shor-Posner G; Lai S; Zhang G; Lai H; Fletcher MA; Sauberlich
H; Page JB
Department of Psychiatry and Behavioral Sciences, University of Miami,
School of Medicine, Florida 33136, U.S.A.
J Acquir Immune Defic Syndr Hum Retrovirol, 15(5):370-4 1997 Aug 15
To determine the independent contribution of specific immunologic and
nutritional factors on survival in HIV-1 disease, CD4 cell count,
antiretroviral treatment, plasma levels of vitamins A, E, B6, and B12
and minerals selenium and zinc were considered in relation to relative
risk for HIV-related mortality. Immune parameters and nutrients known
to affect immune function were evaluated at 6-month intervals in 125
HIV-1-seropositive drug-using men and women in Miami, FL, over 3.5
years. A total of 21 of the HIV-1-infected participants died of
HIV-related causes during the 3.5-year longitudinal study. Subclinical
malnutrition (i.e., overly low levels of prealbumin, relative risk [RR
= 4.01, p < 0.007), deficiency of vitamin A (RR = 3.23, p < 0.03),
vitamin B12 deficiency (RR = 8.33, p < 0.009), zinc deficiency (RR =
2.29.1, p < 0.04), and selenium deficiency (RR = 19.9, p < 0.0001) over
time, but not zidovudine treatment, were shown to each be associated
with HIV-1-related mortality independent of CD4 cell counts <200/mm3 at
baseline, and CD4 counts over time. When all factors that could affect
survival, including CD4 counts <200/mm3 at baseline, CD4 levels over
time, and nutrient deficiencies were considered jointly, only CD4
counts over time (RR = 0.69, p < 0.04) and selenium deficiency (RR =
10.8, p < 0.002) were significantly associated with mortality. These
results indicate that selenium deficiency is an independent predictor
of survival for those with HIV-1 infection.

The distribution of selenium and mortality owing to acquired immune
deficiency syndrome in the continental United States.
Cowgill UM
University of Colorado at Boulder' Department of EPO Biology'
Carbondale 81623' USA.
Biol Trace Elem Res, 56(1):43-61 1997 Jan
A hypothesis has been proposed that selenium (Se) concentration in the
environment as measured by its uptake by alfalfa' which sorbs Se from
the soil in proportion to what is present' exerted an apparent effect
on incidence of (acquired immune deficiency syndrome) AIDS such that
AIDS` mortality within the conterminous United States was lower where
the Se quantity in the soil was high than where the amount was low. The
obJect of this study was to test this hypothesis for statistical
significance and to discover whether the apparent pattern of AIDS
mortality in relation to Se distribution holds true with respect to all
ages' both races (Black and White)' and both genders. The statistical
analysis employed was analysis of variance. Age-specific data as well
as age-adJusted data were subJect to statistical analysis. Ages where
AIDS mortality rates per 100'000 were greatest were in the range from
25-54 yr for low-' medium-' and high-Se areas of the US. Black
mortality owing to AIDS showed highly statistically significant results
for the three Se regions' both genders' and six age groups' whereas
White mortality was not as significantly affected by Se. A hypothesis
is proposed that the Black population during the last decade or so has
been less migratory than the White population. Thus' their food supply
and hence its Se content have been more stable than that of the White
population' which is more prone to consume imported foods to unknown Se
content and be more migratory. A second hypothesis is advanced that
suggests that medical care is not equally available to the poor and
especially poor Blacks. Black men and women die at a greater death rate
than do Whites. This implies that a lack of medical care is the true
cause. This article suggests that a pattern exists between the
geographical distribution of Se using alfalfa as a dietary guide and
AIDS` mortality such that an inverse relationship persists between Se
quantity in an area and AIDS` mortality in the same area.

Supplementation with selenium restores age-related decline in immune
cell function.
Roy M; KiremidJian-Schumacher L; Wishe HI; Cohen MW; Stotzky G
Basic Science Division' New York University Dental Center' New York
10010' USA.
Proc Soc Exp Biol Med, 209(4):369-75 1995 Sep
This study examined the effect of dietary (2.00 ppm for 8 weeks)
supplementation with selenium (as sodium selenite) on the ability of
lymphocytes from aged (24-month-old)' male' C57BL/6JNIA mice to respond
to: (i) stimulation with mitogen (phytohemagglutinin) or alloantigen;
(ii) develop into cytotoxic effector cells; and (iii) destroy tumor
cells. Supplementation with selenium resulted in a significant increase
in the ability of spleen lymphocytes from aged animals to undergo
blastogenesis' as indicated by significantly higher amounts of nuclear
incorporation of 3H-thymidine after stimulation with mitogen. The
dietary regimen restored the age-related deficiency of the cells to
respond to stimulation by nuclear DNA synthesis and cell proliferation'
at least' to the level of cells from unsupplemented young adult
animals. Furthermore' populations of in vivo' alloantigen-activated
lymphocytes from Se-supplemented aged animals contained significantly
higher numbers of cytotoxic lymphocytes than those from Se-normal aged
animals' which resulted in an enhanced capacity to destroy tumor cells.
The significant increase in the number of cytotoxic effector cells
within these activated T-lymphocyte populations was probably the result
of an enhanced clonal proliferation of cytotoxic precursors cells'
followed by the differentiation of greater numbers of cytotoxic
effector cells. This effect occurred in the absence of changes in the
ability of the cells to produce IL-2' which confirmed our earlier
observation that dietary supplementation with selenium does not affect
the production of IL-2. The data suggested that selenium restores the
age-related defect in cell proliferation through an increase in the
number of high-affinity IL-2 receptors.

Trace elements and protein-calorie malnutrition in the F`es area
Squali Houssa ini FZ; Iraqi MR; Arnaud J; Richard MJ; Favier A
Facult]e des Sciences Dhar Mehraz, Morocco.
Biomed Pharmacother, 51(8):349-51 1997
Copper and selenium are essential micronutrients for development and
growth as well as being necessary for the immune system and as an
antioxidant defense. These trace elements present a variable
distribution according to geographic regions. Several studies have
shown reduced serum copper and selenium levels, as well as the activity
of erythrocyte copper-zinc superoxide dismutase (SOD) and
selenium-glutathione peroxidase (GPX) in protein-calorie malnutrition
(PCM). The aim of this study was to evaluate the erythrocyte enzymatic
activity depending on copper or selenium and the levels of these
elements in serum. Fifty-six Moroccan children between the age of 6 to
60 months were selected, then divided into 20 control group children
and 36 patients suffering from PCM (15 mildly malnourished and 21
severely malnourished). The malnourished group showed a significant
decrease of selenium and copper levels that was related to the severity
of malnutrition. Serum selenium decreased more than serum copper. No
differences were noted between the groups in erythrocyte GPX activity,
whereas SOD activity showed more discrepancy than in the copper levels
in malnutrition. Serum copper or ceruloplasmin levels could be used as
indicators of the severity of malnutrition, whereas the selenium levels
could be used as indicators of the nutritional status.

Effect of selenium administration on various laboratory parameters of
patients at risk for sepsis syndrome
Lehmann C; Egerer K; Weber M; Krausch D; Wauer H; Newie T; Kox WJ
Klinik f ur Anaesthesiol]ogie und Intensivtherapie, Universit
atsklinikum Charit]e, Humboldt-Universit at zu Berlin.
Med Klin, 92 Suppl 3():14-6 1997 Sep 15
BACKGROUND: Low selenium plasma levels were often measured in ICU
patients with polytrauma, major surgery or various severe diseases.
Activation of selenium-dependent functions of the antioxidant
metabolism and the immune system is suggested to be causally. METHODS:
In a prospective randomized clinical trial including 24 critically ill
patients we investigated the plasma levels of selenium,
malondialdehyde, glutathione, elastase, fT3, fT4, TSH, IL-2R, IL-6 and
IL-8 with and without parenteral selenium supplementation for 3 weeks
(study design: week 1: twice 500 micrograms daily, week 2: once 500
micrograms, week 3: three times 100 micrograms sodium selenite).
RESULTS: Following 24 hours of supplementation selenium plasma levels
were normalized. Malondialdehyde level decreased in the therapy group
significantly beginning at day 3. In the control group we observed
increased malondialdehyde values, a disturbed glutathione metabolism
and an elevated elastase activity. fT3-values were diminished at day 0
in all patients. In the therapy group we measured a gradual fT3
restoration. In the control group a reactive TSH increase was observed.
selenium supplementation did not lead to an excessive stimulation of
IL-2R, IL-6 or IL-8. CONCLUSIONS: 1. Rapid normalization of selenium
plasma levels can be achieved with the applied selenium dosage. 2.
Parameters of radical metabolism are significantly reduced following
selenium administration. 3. T3 synthesis correlates closely with the
selenium levels. 4. Excessive stimulation of the immune system does not
appear in the applied dosage.

Increased virulence of coxsackievirus B3 in mice due to vitamin E or
selenium deficiency.
Beck MA
Frank Porter Graham Child Development Center' University of North
Carolina' Chapel Hill 27599-8180' USA.
J Nutr, 127(5 Suppl):966S-970S 1997 May
Nutrition has long been known to affect the ability of the host to
respond to infectious disease. Widespread famines are often accompanied
by increased morbidity and mortality due to infectious diseases. The
currently accepted view of the relationship between nutrition of the
host and its susceptibility to infectious disease is one of a direct
relationship with host immune status. That is' if the nutritional
status of the host is poor-due to either single or multiple nutrient
deficiencies-then the functioning of the host immune system is
compromised. This impairment of the immune response will lead to an
increased susceptibility to infectious disease. Clearly' the immune
response has been shown to be weakened by inadequate nutrition in many
model systems and in human studies. However' what about the effect of
host nutrition on the pathogen itself? Our laboratory has shown' using
a mouse model of coxsackievirus-induced myocarditis' that a host
deficiency in either selenium or vitamin E leads to a change in viral
phenotype' such that an avirulent strain of the virus becomes virulent
and a virulent strain becomes more virulent. The change in phenotype
was shown to be due to point mutations in the viral genome. Once the
mutations occur' the phenotype change is stable and can now be
expressed even in mice of normal nutriture. Our results suggest that
nutrition can affect not only the host' but the pathogen as well' and
demonstrate a new model of relating host nutritional effects to viral

selenium: a quest for better understanding.
Badmaev V; MaJeed M; Passwater RA
Sabinsa Corporation' Piscataway' NJ' USA.
Altern Ther Health Med, 2(4):59-62' 65-7 1996 Jul
selenium is an essential trace element in nutrition for the prevention
of disease in humans. Epidemiological studies indicate an association
between low nutritional selenium status and increased risks of
cardiomyopathy' cardiovascular disease' and carcinogenesis in various
sites of the body. The role of selenium supplementation in the
prevention and treatment of AIDS-related pathology has been considered.
Selenoproteins discovered in mammalian cells may account for the
essentiality of selenium in the body`s antioxidant defense; thyroid
hormone function; immune system function' particularly the cellular
immunity; formation of sperm; and functioning of the prostate gland.
The seleno-organic compounds' primarily L-(+)-selenomethionine'
generally are recognized as safe and effective forms of selenium
supplementation. The nutritionally recommended dose of elemental
selenium is estimated at 50 to 200 mg per day. There is' however'
increased discussion of a pharmacological dose of selenium'
significantly higher than the nutritional dose of the microelement' to
treat active conditions. One way of increasing the tissue levels of
selenium is to combine its ingestible form with a nutrient
bioavailability enhancing compound.

Nutritional modification of inflammatory diseases.
Schoenherr WD; Jewell DE
Mark Morris Institute' Topeka' KS' USA.
Semin Vet Med Surg (Small Anim), 12(3):212-22 1997 Aug
Regulation of the immune system is extremely complex. We are only
starting to understand how the immune system coordinates the body`s
response to a disease or invading pathogen. Immunomodulation' as the
term implies' can be used to designate either a suppression or an
augmentation of an immune response. Suppressing the function of the
immune system may be important in cases of inflammation and augmenting
the immune response when increased resistance to disease is required.
Nutrition does and can play an important role in modulation of the
animal`s immune system. The maJority of scientific literature published
on the interaction of nutrition and the immune system correlates the
effects of nutrient deficiency and modulation of an immune response.
These studies have evaluated deficiencies of protein; energy; the fat
soluble vitamins A' D' and E; the B-complex vitamins; vitamin C; and
the minerals selenium' iron' zinc' and copper and their relationship to
immune dysfunction. Most recently' researchers have concentrated
efforts on evaluating the impact specific fatty acids have on
modulation of the immune system. Undoubtedly' the nutritional status of
the animal plays an important role in resistance mechanisms against
disease causing organisms and may influence the outcome of disease in
infected animals. The focus of this chapter is to concentrate on the
role specific polyunsaturated fatty acids have on the immune response
of animals and to consider the potential for nutritional modification
of diseases related to inflammation.

Nutritional biochemical aspects of the significance' of the
utilization' of metabolism and of the administration of vitamin E and
of selenium in sheep (review)
Kolb E; Kaskous S; Seehawer J
Veterin ar-Physiologisch-Chemisches Institut' Universit at Leipzig.
Berl Munch Tierarztl Wochenschr, 110(5):178-84 1997 May
A review is given on the significance' availability' metabolism and
application of vitamin E and selenium in sheep. Vitamin E deficiency
commonly occurs in spring. selenium deficiency occurs in certain areas
where the selenium content of plants is low. A further factor is the
low availability of selenium as a consequence of reduction reactions in
the forestomachs. When the supply of vitamin E and selenium is
suboptimal' activity of the immune system and growth are impaired.

selenium and cellular immunity. Evidence that selenoproteins may be
encoded in the +1 reading frame overlapping the human CD4' CD8' and
HLA-DR genes.
Taylor EW
Computational Center for Molecular Structure and Design' University of
Georgia' Athens 30602-2352' USA.
Biol Trace Elem Res, 49(2-3):85-95 1995 Aug-Sep
selenium deficiency can lead to impaired immune function and reduced
T-cell counts' as well as various specific disorders. Significantly' in
ARC and AIDS patients' a progressive decline in plasma Se' paralleling
T-cell loss' has been widely documented. Since evidence now suggests
that there is an extremely high turnover of CD4+ T-cells in AIDS
patients' with billions of new cells lost and replaced daily' any
exceptional requirement for Se in lymphocytes could contribute to this
progressive Se depletion. Thus' it may be significant that' overlapping
the known genes in the +1 reading frame' the mRNAs of several T-cell
associated genes (CD4' CD8' HLA-DR p33) have open reading frames (ORFs)
with as many as 10 in-frame UGA codons (CD4' p33)' a clustering that is
highly improbable by chance alone' and reminiscent of selenoprotein P'
the predominant plasma form of Se. The presence of these ORFs' along
with potential stem-loop RNA structures displaying consensus
selenocysteine insertion sequences' AUG(N)mAAA(N)nUGR' suggests that
these mRNAs may encode selenoproteins' in addition to the known T-cell
glycoproteins. If so' the roles of Se in the immune system may be more
diverse than previously suspected.

Reactive oxygen species in the pathogenesis of gastrointestinal
tumors. A follow-up study
Zimmermann T; Albrecht S; Lauschke H; Ludwig K
Klinik f ur Thorax-' Viszeral- und Gef asschirurgie' TU Dresden.
Med Klin, 90 Suppl 1():15-8 1995 Jan 15
Development and growth of gastrointestinal tumors seems to correlate
closely with the formation of reactive oxygen intermediates (ROI). It
is known' that oxygen-free-radicals are able to induce a precancerous
stage and tumor growth by damaging DNA or changing the protein and
lipid structure. To investigate' whether the cellular formation of
oxygen-free radicals plays a role in the pathogenesis of colorectal
carcinoma' we performed the study presented here. 40 patients with
colorectal carcinoma were studied over a period of 6 months (before
operation' 10 days after operation' 3 months later' 6 months later).
Oxygen-free radicals were determined by chemiluminescence response in
the whole blood' in granulocytes and in monocuclear blood cells (MBC).
At the same time the trace elements selenium' Copper and Zinc' known to
play an important role as antioxidants' were measured. RESULTS: We
observed' that the ability of granulocytes for phagocytosis was
depleted. However' this effect could be reversed as demonstrated in in
vitro stimulation assays. After 6 months the phagocytosis by
granulocytes achieved again normal values. Simultaneously a dramatic
increase in superoxide-anions generated by mononuclear blood cells was
seen. This increase was still obvious after 6 month. Independent of the
tumor state selenium deficiency was found in all patients. Since no
substitution of selenium was performed after operation' this deficiency
was not normalised. CONCLUSION: The ability for phagocytosis and
therefore the immune response is reduced in a reversible manner. In
addition reactive superoxide-anions' that are able to induce tumors'
are formed. This risk is increased in the absence of selenium. Thus'
clinical follow-up studies are needed to determine subclinical tumor
relapses and to investigate the role of oxidative stress by
chemi-luminescence. As consequence of this study selenium substitution
seems to be indicated.

Nutrition and the immune system: a review of nutrient-nutrient
Kubena KS; McMurray DN
Department of Animal Science and Faculty of Nutrition' Texas A&M
University' College Station 77843' USA.
J Am Diet Assoc, 96(11):1156-64; quiz 1165-6 1996 Nov
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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