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Stress, Drugs and Immunity
By Linda Aronson, DVM

The immune system is an interactive
network of cells and proteins designed
to protect the body from pathogens in
the environment, parasites, malignant
cells, allergens and toxins. The system
has specific and non-specific moieties
to protect and serve. The latter includes
the barriers of skin and mucous
membranes, non specific Natural Killer
(NK) cells that destroy anything that
isn’t self, phagocytes – cells that engulf
and neutralize anything alien and various
chemical defense mechanisms.
Other cells are produced in response to
a particular invader. In the blood we
circulate antibodies (immunoglobulins)
produced by B cells that neutralize specific
viruses and toxins. Together with
“complement” proteins they also destroy
and clear out invading bacteria.

The bone marrow makes large macrophages
– big eating machines - and B
cells, while the thymus gland in the
neck produces T-cells (there are three
types, one turns on B-cells, another
turns on the third type of T-cells the
ones that destroy virus and tumor infected
cells). Like any army, the immune
system needs to coordinate and
communicate, and it does so through
hormone like substances called cytokines
– including interleukins (ILs),
interferon (INF) and tumor necrosis
factor (TNF). Psychological stress
causes sleep disturbances, decreased
appetite and delays wound healing.
Restraint, isolation and physical manipulation
are very stressful to animals.
Unfortunately, going to the vets tends
to involve many of these stressful procedures
and in an already sick dog may
contribute to a worsening of his condition.
Vets can help minimize the stress
by making sure pets that require hospitalization
are kept in adequately sized
cages, that floors are dry, the environment
is comfortable and clean and at an
optimal temperature, noise should be
minimized; species kept separately,
water and food of good quality and
appropriate for the animal’s condition
provided, and periods of light and dark
maintained so that the dog’s normal
patterns of rest and sleep aren’t disturbed.
Many vets will provide Dog
appeasing pheromone diffusers, pheromones
mimicking those produced by
bitches when they nurse their puppies,
and which calm and comfort many agitated
dogs. Owners who have trained
their dogs to accept all manner of handling
and have them crate trained while
they are healthy can help minimize the
stress their dog experiences when being
examined or hospitalized. Physical
stress – surgery and trauma – as well as
psychological stress result in suppression
of the immune system.
As we might expect surgical trauma
causes a reduction in the immune response,
however - beyond the physical
stress, the psychological stress and the
pain often present before but also involved
in the surgery - anesthesia itself
causes immunosuppression. These
multiple stresses to the system can lead
to postoperative problems – hypothermia,
low blood pressure, increased
pain, sleep difficulties, impaired respiration,
increased cardiac demand, gastrointestinal
problems – ulcers and/or
loss of normal motility - as well as loss
of appetite, weight loss, delayed healing,
infection and growth of malignant
Controlling pain before, during and
after surgery is of paramount importance.
It has been shown that the more
pain an animal experiences, the more
likely that any tumor present will metastasize.
Most effective in blocking
endocrine metabolic responses is the
use of analgesics applied to nerves
serving the surgical site – nerve blocks,
spinal and epidural anesthesia. Local/
regional anesthesia can abolish surgical
stress. Maintaining the block post surgically
can further reduce immunosuppression
and speed healing. Opioids
and non steroidal anti-inflammatory
drugs (NSAIDs) have little effect in
reducing stress at recommended doses,
although they do reduce inflammation,
which infiltrative anesthetics do not
affect. Some immune cells however,
have opioid receptors; and T and perhaps
B cells can produce opioid immunopeptides
– beta-endorphin, enkephalin
and dynorphin. Local application
of opioids is far less likely to
produce immunosuppression, and can
be very helpful in treating such conditions
as arthritis.
Other preoperative strategies that may
help reduce surgical stress are a single
dose of glucocorticoids; in patients
with heart disease beta blockers are
helpful; adequate nutrition, especially
feeding carbohydrates, may stop the
body breaking down muscle and other
Hypothermia is a threat to surgical patients
on several fronts. Immunosuppression
makes the body more susceptible
to bacterial infections. Blood vessels
constrict near the skin, and reduce
blood flow that is needed for repair of
damaged tissues and further decreases
the activity of local immune defense
factors. Neutrophil – white blood cell
– function is compromised so they are
less effective at eliminating bacteria,
the production of cytokines and reproduction
of T cells is also reduced.
Even a central hypothermia of 1.9oC
tripled the incidence of surgical wound
infections in one study. Lowered blood
pressure, as a result of blood loss and
various anesthetic agents, further exacerbates
these problems.
The longer the animal is anesthetized
and surgery lasts, the greater the risk of
infection of the wound and respiratory
infection. One study showed that in
surgeries lasting less than an hour, the
concentration of B and T cells took
about 7 days to return to normal, but
for longer surgeries the return to normal
took significantly longer.
Because of the immunosuppression
produced by anesthesia and surgery,
vaccinations should not be given at the
time of surgery, and elective surgery
should be delayed at least 3 weeks after
vaccination. This must obviously be
weighed against further stress when
dealing with wild or feral animals, but
in the domestic dog there is no medical
excuse to vaccinate an animal at the
time of surgery. This practice can not
only diminish the immune response to
and efficacy of the vaccine, but is more
likely to result in anaphylactic
(allergic) reaction, thrombocytopenia
(lowering of platelets and risk of bleed-

ing). Anaphylactic reactions are often
fatal, and may be delayed up to 48
hours. Modified live vaccines (MLV)
are particularly associated with thrombocytopenia,
which could obviously be
dangerous and lead to excessive post
operative bleeding and other complications.
The use of NSAIDs and some
other drugs could worsen these complications.
Dogs with undiagnosed von
Willebrand’s disease or hemophilia
would be at particular risk. MLVs may
also induce a mild viral infection, fever,
anorexia and lethargy, all of which
would be more serious in the post surgical
Similarly, elective surgery should never
be performed on dogs that are sick. In
the case of emergency surgery all efforts
must be made to reduce both surgical
and psychological stress in the
debilitated animal. While there has
been some disagreement between various
studies, there is evidence that anesthesia
and surgery do make metastasis,
particularly to the lung, of tumors more
likely. Because morphine decreases
natural killer efficacy there may be
increased growth of tumors post surgically
if opioids are used for pain relief.
However, even worse is providing no
pain relief as this really promotes tumor
Surgery, even simple tooth cleaning
and other minimally invasive practices,
is not to be taken lightly. At some time
or other most of our Beardies are going
to have to be anesthetized and I hope
that this article has clarified why we
need to look at the general health of a
dog – including looking at the CBC and
biochemistry profile – before we consider
elective surgery. Because of the
immunosuppression we need to bolster
the dog’s natural immunity, and antibiotics
may be started even before surgery
begins. Always make sure your
vet knows about any medical conditions
your dog has, because this may
affect the choice of appropriate drugs
to use for anesthesia and pain relief.
Make sure your Beardie is given pain
relief; he will heal better and faster.
Never agree to vaccinations being
given at the time of surgery. Most important
of all, before your dog ever
needs surgery, make sure he is comfortable
with different situations and being
handled by strangers. Make sure he is
used to being crated. If you do this you
will have done your best to ensure his
well-being when he is sick, so that he
can come through medical procedures
and surgery with minimal stress and a
much healthier immune system to
speed his recovery.


A big thank you to Dr. Aronson for her contribution to PON Digest