.
Vol. '2a No.1
Spring 1996
SALT U
Trace Minerals
for the ANIMAL NUTRITION
Published by the SALT INSTITUTE
PROFESSIONAL
Trace Minerals: Keys to IlDlDunity
by Larry L. Berger, Ph.D.
Immunology is not a new science. In
1718, an English physician Edward
Jener documented the fact that milkmaids who contracted cowpox were
then immune to smallpox. German scientists in 1890 were the first to illustrate the mechanisms of immunity by
showing that blood serum taken from
animals immunized against diphtheria
could be used to transfer this immunity
to unimmunized animals. In the 1930s
the term "antibody" was coined to described the antitoxins in serum that
caused the neutralization and precipitation of toxins and lysis of bacteria. In
the past few years there has been a
great deal of research published showing the key role of trace minerals in
maximizing immunological function.The
purpose of this review is to update the
nutrition professional to our current level
of understanding concerning the role of
copper, iron, selenium,chromium,cobalt
and zinc in the immunesystem.
major cell type involved is the lymphocyte, which can be found free in tissues
or blood, or concentrated in distinct organs like spleen, lymph nodes, and thymus gland. Depending on the organ of
origin, the lymphocytes will differentiate
to become B-cells or T-cells. Upon antigenic stimulation, these cells will produce specific antibodies that destroys
the antigen.
Trace mineral requirements are determined largely by animal growth or
reproductive response, and not by the
ability of the immune system to respond to a challenge. Usually, efforts
are made to minimize exposure to antigens during the feeding studies used to
determine trace mineral requirements.
There is increasing evidence that the
concentrations
of trace minerals required for healthy animals are often below what is required for animals experiencing an immunological
challenge.
Consequently, this review will focus primarily on experiments where the trace
mineral concentrations are above what
Immune Function
would be present in the basal diet.
To understand how trace minerals affect immune competency,a brief review
of immune system function is in order.
The purpose of the immune system is
to render harmless a foreign agent
which may be a bacterium, protozoan,
virus or noninfectious entity such as a
chemical or toxin. The immune system
uses several methods to detoxify these
foreign agents or antigens. For example, phagocytosis is a nonspecific immune response in which a particle is
engulfed by a phagocyte and subsequently digested. Phyagocytes are
present in the spleen, liver, and lung,
and circulate in the blood.
In contrast to the phagocytic system,
which lacks specificity and memory to
an antigen, the lymphoid organ dependent immune system develops different antibodies for each antigen. The
Copper
Copper level in the diet has been
shown to affect the resistance of sheep
to bacterial infections (Woolliams et aI.,
1986). The Scottish Blackface hill breed,
which is naturally susceptible to copper
deficiency, is highly vulnerable to microbial infections. Copper supplementation has increased their resistance
and survival rate. In one study with 65
Iambs, death losses varied from 2 to
10% in Iambs with less than 3.0 micromoles of copper per liter of blood, while
there were no losses in Iambs with
greater than 4.0 micromoles of copper
per liter of blood. In these studies, copper deficiency did not decrease the
prevalence of microbial infection, but it
did decrease mortality. Infections, found
mainly in the gastrointestinal tract and
lungs, apparently were more damaging
because of enhanced inflammatory reactions when the Iambs were copper
deficient.
Resistance to internal parasites is
also compromised
with copper deficiency. For example, Hucker and Yong
(1986) found that copper deficient
Iambs inoculated with t. axei and t. colubriformis had maximum
fecal egg
counts 2 weeks sooner and became
more hypoalbuminemia than Iambs receiving supplemental copper. The infection also reduced plasma copper levels
in the deficient Iambs, but not in the
copper supplemented Iambs. In Iambs
grazing areas with a parasite load, having adequate copper in the diet is a key
to controlling the worm burden.
- continued next page
.
ASK
DR. BERGER
Q. Wh.iph mi.oeral$?$houJ~ I be concerne~ with to prevent grass tetany .in
my lactating beef cows?
A. The best way to prevent grass tetany is to feed free-choice a mixture of equal
parts magnesium oxide: trace mineral salt and grain (corn, barley, etc) beginning .two y,reeks t:>eforethe cows a(e turned out to pasture. The disease is
caused by excess potassiu mih the fOrage which prevents magnesiuQ71absorption. Magnesium oxide willprovide the magnesium and the salt willincrease the
sodium:potassium ratio in the rumen which improves magnesium absorption.
Q. Can I use a trace mineralized salt designed for beef cattle to feed my 4H Iambs?
A. It depends on the copper level in the trace mineral salt and the diet you are
feeding. To be safe, the total diet for sheep should be under 10 ppm copper.
Sheep are more susceptible to copper toxicity at levels which may just meet
the needs of cattle.
Q, Do horses exhibit "nutritional wisdom"? When given a choicewill ttley
select the appropriate amounts of each mineral, if I offer a variety of
mineral sources cafeteria style?
A. Generally, animals do not have the ability to consume only the amount required top:'\eetth~ir need forgiven minerals. Also, maQYof the puremineral
forms are not very palatable, and will not be consumed readily unless mixed
with the other feedstuffs. It is more likely your horse will get the balanced
nutrition you desire if you feed a balanced mineral supplement mixed with
the rest of the diet.
Q. Does particle size affect salt's ability to act as an intake regulator for
lARRY L BERGER, Ph.D.
PROFESSOR
OF ANIMAL SCIENCES
UNIVERSITY
OF ILLINOIS
It is widely recognized that feeder
cattle from copper deficient areas are
less responsive to vaccinations for diseases associated with shipping fever
compared to cattle that have had adequate copper. Diets that are high in molybdenum and sulfur can compromise
the copper status of cattle by forming
insoluble complexes in the rumen.
Ward et al. (1993) reported that prolonged exposure to molybdenum (10
ppm) and sulfur (0.2% sulfur) decreased in vivo cell-mediated immune
function in feeder cattle. The lower (P
<.10) in vitro viability of lymphocytes
collected from steers receiving the molybdenum and sulfur suggests that these
cells are morefragile.These researchers
interpreted their data to suggest that cellmediatedimmunityis more susceptibleto
molybdenumand sulfursupplementation
(decreased copper availability) than is
humoral
immunity.
Because many factors affect the responsiveness of the immune system,
there are trials where copper deficiency
has not had much effect (Stabel et al.
1993). However these same researchers indicated, that "viral and bacterial challenge of cattle can cause a
rapid transient increase in serum ceru-
2
free-choice supplements being fed to cattle while grazing?
A. Yes. Usually a finer grind of salt work best. This is especially true if the supplements are in the meal form. If the supplement is pelleted, salt particle
size may opt make much difference;
loplasmin and plasma copper in copperreplete animals, suggesting a major protective role for copper in infectious diseases." These researchers also showed
that copper concentrations in organs critical to the immune system such as the
liver, spleen, thymus, and lung were substantially reduced by copper deficiency.
These data help explain why copper deficient cattle are at greater risk for infection
than are the copper supplemented cattle.
Iron
Iron is an interesting trace element in
that either a deficiency or an excess
can compromise the immune system. It
has been well documented that serum
iron falls early in response to bacterial
and viral infections
and rebounds
quickly with recovery. This hypoferremia
is believed to be an important protective component of the acute phase response to infection. With Pasteurella
haemolytica, a major respiratory pathogen of cattle and sheep, the iron-regulated cell wall proteins have been identified as important vaccine components
because of their antigenicity. If iron is in
great excess, then the key proteins required to initiate recognition and antibody production may be masked.
This does not mean that iron deficiency resulting in anemia will enhance
immunity. To the contrary, anemic animals are much more susceptible to infections than those with adequate iron.
Once the infection is established, iron
supplementation has been shown to increase the bactericidal activity of liver
and splenic marcrophages. For example, chicks inoculated with S. Gallinarum had increased (P <.01) survival
when iron (100 ppm of diet or more)
was added to a basal diet containing
200 ppm of iron. Anemia was found in
the diseased chicks three days post-infection and continued through day nine
as measured by decreased hemoglobin
and hematocrits. However birds receiving additional iron, up through 600 ppm,
had less severe anemia and increased
antibody titres. These and other data in
broilers show that once the infection has
occurred, increased supplemental iron
enhances the immune system in destroying the invading organism.
Selenium
Selenium is recognized as an immonostimulant in swine, poultry and ruminants. Often selenium and vitamin E
are supplemented together because
SALT 8 Trace Minerals / Spring 1996
.
.
they play similar physiological roles.
However, recent research has shown
that their effects are additive when
measured as immune response in pigs.
Peplowski et al. (1980) measured humoral antibody production to sheep red
blood cells in weanling pigs receiving
selenium and/or vitamin E. Pigs were
fed a basal diet to which 0 or 0.5 ppm
of selenium and 0 or 220 IU of vitamin
E / kg were added. The basal diet contained 0.02 ppm selenium and 7 mg of
alpha-tocopherol/kg. Humoral antibody
titres were increased (P <.01) when
either selenium or vitamin E were added
alone, and were further increased (P
<.01)when both nutrientswere added.
Colnago et al. (1984) challenged
male broiler chicks with E. tenella 00cysts from 22 to 32 days of age in six
experiments to determine if selenium
would affect the ability of the bird to
cope with coccidiosis. Graded selenium
levels from 0.1 to 1.0 ppm or 100 ppm
of vitamin E/kg were added to the diet
from day one of age. Dietary supplementation of at least 0.25 ppm selenium or vitamin E reduced mortality (P
<.05) and increased weight gains (P
<.05). These authors showed that feeding 0.25 ppm selenium or more, increased leucocyte numbers in the
blood after infection with coccidia and
may explain the immune enhancement.
Boyne and Arthur (1981) reported
that neutrophils from selenium-deficient
calves had a decreased ability to kill ingested Candida albicans compared to
neutrophils from seleniumsupplemented
calves.The authors linkedthe decreased
effectiveness of the neutrophils to reduced glutathione peroxidaseactivity resulting from selenium deficiency.When
glutathione peroxidase activity is reduced, peroxide and lipid hydroperoxide
tend to accumulate to toxic levels in the
neutrophils. In these trials the calves
were fed diets containing 0.01 mg selenium/kgfor six monthsbeforeglutathione
peroxidaseactivitywas reduced.
Rate of clinical mastitis was negatively correlated to plasma selenium
concentration in nine well-managed
dairy herds in Ohio (Weiss et al. 1990).
Plasma selenium was positively correlated to selenium intake by cows up to
5 mg selenium per day, and was independent at higher intakes. The role of
vitamin E is also important in that high
intakes of selenium without adequate
vitamin E did not reduce mastitis. The
exact mechanism by which these two
nutrients interact to reduce mastitis is
quite complicated and requires additional research.
Chromium
Recent
Canadian
research
has
shown that chromium is most beneficial
in high-stress periods. Shipping stress,
for example, will often impair the immune system and make animals more
susceptible
to invading pathogens.
Chang and Mowat (1992) evaluated the
effects of supplemental chromium, from
high-chromium yeast, on the performance and health of stressed calves with
or without long-acting oxytetracycline.
During the first28 days after shipping,
feeding 0.4 ppm chromium increased
averaged daily gains (1.34 vs. 1.74
Ib/day) and gains per unit of dry matter
intake (0.123 vs. 0.156) in calves not receiving oxytetracycline. However, chromium supplementation had no effect on
performance of calves receiving the antibiotic. Calves in this trial were stressed in
that they were transported by truck for 18
hours, rested and offered hay and water
for 10 hours, and then transported an additional 26 hours before arrival. It is likely
that this level of stress increased urinary
chromium excretion and depleted body
chromium stores. Stress often causes
caused
increased
anti-ovalbumin
re-
sponse (P <.01) but did not affect the
immune response to the red blood
cells. These data suggest that chromium supplementation
may enhance
resistance to mastitis in dairy cows.
The exact mechanism by which chromium enhances the immune system is
not known. However, one of the consistent results of the studies was that chromium reduced serum cortisol levels. Glucocorticods, which include cortisol, are
known to suppress the immune system.
Whether the organic forms of chromium are required to stimulated the immune response is unknown. It is known
that organic forms are absorbed 5 to 10
times more effectively than chromium
chloride, which is absorbed at 3% or
less. However, because small concentrations are required, chromium chloride may be an economical source in
many diets. Additional research is also
needed to determine if the same stimulatory effects on the immune system
can be obtained in swine and poultry.
Cobalt
Fisher and MacPherson (1986) reported that cobalt deficiency rendered
sheep more susceptible to bacterial infections. Of eight Iambs in the severely
deficient groups (B12 100 pg/ml or less),
seven succumbed to microbial infections.
increased glucose mobilization which
increases mobilization
of chromium
from body stores.
In a second study, Monnsie-Shageer
and Mowat (1993) fed 0,0.2,0.5, and 1
ppm supplemental chromium from highchromium yeast, to 84 Charolais-crossed
feeders stressed due to shipment. Chromium supplementation decreased morbidity (P <.05) and rectal temperature at
day 2 and 5 after arrival. Peak antibody
titers to human red blood cells and immu-
In contrast, none of the eight on the adequate cobalt treatment died. Reductions
in candidacidal activity of ovine neutrophils have been reported as a result of
cobalt deficiency. These authors noted
that the changes in the health of the neutrophils became evident before vitamin
B12 status decreased.
noglobulin G1 concentrations were increased (P <.07) due to chromium supplementation. The basal corn silage diet
contained 0.16 ppm chromium.
In a third experiment, the effects of
supplemental chromium on immune responses of dairy cows subjected to
physical and metabolic stresses associated with late pregnancy, calving, and
peak milk yield were determined.
Chelated chromium (0.5 ppm) was fed
beginning six weeks prepartum and
continued through 16 weeks postpartum. To measure humoral immune responses, all cows were immunized with
ovalbumin and human red blood cells
Substantial evidence has been reported that adding zinc above the supposed requirement enhances disease
resistance in chickens. Southern and
Baker (1983) reported that adding 50
ppm zinc to broiler diets containing 40
ppm zinc increased (P <.05) gain and
feed efficiency when infected with E.
acervulina. Coccidiosis caused a decrease in liver zinc concentrations.
Stahl et al. (1984) reported that the
immunocompetence of progeny chicks
from hens was affected by dietary zinc.
White Leghorn breeding hens were fed
a corn-soy diet supplemented with 0,
10, 20, 40 or 150 ppm zinc. Progeny
approximately two weeks before and
two weeks after calving. Chromium
SALT a Trace Minerals / Spring I996
Zinc
-continued
next page
3
.
tal chromium on immune response of peri parturient and early
lactation dairy cows. J. Anim. Set.
71:1532.
Chang, X., and D.N. Mowat. 1992. Supplemental chromium for stressed and
growing feeder calves. J. Anim. Set.
70:559.
Salt as a trace mineral
carrier
Colnago, G.L, LS. Jensen, and PL
To maximize immune functions these
Long. 1984. Effect of selenium and
vitamin E on the development of imtrace minerals must be provided on a
munity to coccidiosis in chickens. J.
regular basis. Because many of the
Poultry Sci. 63:1136.
trace mineral compounds are unpalatFisher, G., and A. MacPherson. 1986.
able in the pure from, providing a delivCobalt deficiency in the pregnant
ery method that ensures the proper inewe and Iamb viability. In: Proceedtake on a regular basis is essential. A
well-fortified trace mineralized salt has
ings of the 6th International Conference on Production and Disease in
proven to be the safest, most effective
Farm Animals, pp. 158. Veterinary
delivery method.
Research Laboratory, Stormont, BelIn summary, the immune system is
fast, N. Ireland.
one of the most complex and intricate
Hucker, DA, and WK. Yong. 1986. Efcellular and molecular interactions known
fects of concurrent copper deficiency
in all of biology. Trace minerals act as
and gastrointestinal nematodiasis on
keys which unlock the ability of the imcirculating copper and protein levels,
mune system to ward off invaders. Proper
liver copper and bodyweight in
trace mineral supplementation will not
sheep. Vet.Parasitol. 19:67.
eliminate disease, but it will allow the aniMonnsie-Shageer, S., and D.N. Mowat.
mal's immune system to respond with
1993. Effect of level of supplemental
peak efficiency to minimize the risk of significant economic losses.
chromium on performance, serum
constituents, and immune status of
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stressed feeder calves. J. Anim. Set.
71:232.
Boyne, R, and J.R. Arthur. 1981. Effects of copper and selenium defi- Peplowski, MA, D.C.Mahan, FA Murray, A.L. Moxon, AH. Cantor, and
ciency on neutrophil function in catK.E. Ekstrom. 1980. Effect of dietary
tle. J. CompoPath. 91:271.
Burton, J.L, B.A. Mallard, and D.N.
and injectable vitamin E and selenium in weanling swine antigenically
Mowat. 1993. Effects of supplemen-
from unsupplemented hens had reduce
titers to sheep red blood cells compared to those receiving the 10 and 20
ppm zinc treatments. However, excessive zinc (150 ppm) also depressed the
immunocompetence of the progeny.
,,---
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Address
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Salt Institute
TM
700 North Fairfax Street
Fairfax Plaza, Suite 600
Alexandria, Virginia 22314-2040
Published two times a year. Permission
is granted to reprint material from Salt &
Trace Minerals provided credit is given.
All queries regarding other publications
on the specific uses of salt should be addressed to the Salt Institute, 700 North
Fairfax Street, Fairfax Plaza, Suite 600,
Alexandria, Virginia 22314-2040 or call
(703) 549-4648, fax (703) 548-2194.
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PRINTED
ONRECYCLED
PAPER
Correction
challenged with sheep red blood
cells. J. Anim. Set.51:344.
Stabel, J.R., J'w. Spears, and TT.
Brown, Jr. 1993. Effect of copper deficiency on tissue, blood characteristics, and immune function of
calves challenged with infectious bovine rhinotracheitis virus and Pasteurella hemolytiea. J. Anim. Set:
71:1247.
Stahl, J.L, and M.E. Cook, and M.L
Sunde. 1984. Enhanced humoral immunity in progeny chicks from hens
fed diets supplemented with zinc.
PoultrySei. 63:(Suppl. 1),187.
Southern, LL, and D.H. Baker. 1983.
Eimeria aeervulina infection and
zinc-copper interrelationships in the
chick. Poultry Set.62:401.
Ward, J.D., J.W Spears and E.B.
Kegley. 1003. Effect of copper level
and source (copper lysine vs copper
sulfate) on copper status, performance, and immune response in growing steers fed diets with or without
supplemental molybdenum and sulfur J. Anim. Sci. 71:2748..
Weiss, WP, J. S. Hogan, K.L. Smith,
and K.H. Hoblet. 1990. Relationship
among selenium, vitamin E, and
mammary gland health in commercial dairy herds. J. Dairy Sci. 73:381.
Woolliams, C., N.F. Suttle, J.A. WoolIiams, D.G. Jones, and G. Wiener.
1986. Studies on Iambs genetically
selected for low and high copper
status. I. Differences in mortality.
Anim. Prod. 43:293.
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