INTERNAL MEDICINE
Article reprinted with permission of VETERINARY MEDICINE -
Jul 27, 2017 VETERINARY MEDICINE is a copyrighted publica-
tion of Advanstar. Communications inc. All rights reserved.
Just Ask the Expert:
Is There a Role for Melatonin
in Dogs and Cats with IMHA?
By Christopher G. Byers, DVM, DACVECC, DACVIM
VETERINARY MEDICINE
This hormone is already embraced by some veterinar-
ians for various conditions. Dr. Christopher Byers ex-
plores whether there is an indication for immune-me-
diated hemolytic anemia. Can melatonin be used to
treat immune-mediated hemolytic anemia (IMHA) in
veterinary patients?
Melatonin is a hormone produced in the pineal gland
of the brain. In people, melatonin secretion is influ-
enced by the amount of light to which the body is
exposed. Thus, traditionally it is thought to help reg-
ulate our normal waking and sleeping cycles. For ex-
ample, melatonin levels increase in the evening and
decrease in the early morning. Because of this effect,
many people take oral melatonin supplements to treat
disorders such as insomnia, jet lag and seasonal af-
fective disorder. Many emergency veterinarians use
melatonin to help control their sleep patterns when
working overnight shifts.
Melatonin has been used in limited capacity in veter-
inary medicine. Veterinary dermatologists frequently
prescribe this supplement for patients living with alo-
pecia X. Some internal medicine specialists will initially
use a combination of melatonin and hydroxymataire-
sinol (HMR) lignans to treat occult hyperadrenocor-
ticism, a syndrome biochemically characterized by
normal serum cortisol concentrations with elevated
androgens (i.e. estradiol, 17-OH progesterone, pro-
gesterone, androstenedione) post-ACTH stimulation.
The use of melatonin for immune-mediated diseases
comes from extrapolation from human literature. One
study reported the successful control of refractory id-
iopathic thrombocytopenic purpura in three human
patients after melatonin administration.1This same
group of researchers also documented resolution
of severe hemorrhage due to refractory idiopathic
thrombocytopenic purpura with melatonin admin-
istration.2Current evidence suggests melatonin may
be a helpful non-immunomodulatory therapeutic ad-
junct for patients with immune-mediated thrombocy-
topenia (ITP) because it promotes the fragmentation
of megakaryocytes, thus increasing the number of cir-
culating platelets.
Literature also suggests melatonin may modulate cy-
tokine production, including interleukin-1 (IL-1), IL-2,
IL-6, IL-13 and interferon alpha. One study showed
melatonin decreased IL-6 and IL-13 production, as
well as antagonized specific autoantibodies in a mu-
rine model of systemic lupus erythematosus (SLE).3
Another study showed melatonin administration
appeared to rescue hematopoiesis in mice treated
with anti-cancer compounds through promotion of
endogenous release of granulocyte/macrophage
colony-stimulating factor and opioid cytokines.4 Mel-
atonin appears to directly affect inflammation and im-
mune cells, as well as enhance hematopoiesis.
It is for these reasons some have advocated its use
in the treatment of other immune-mediated condi-
tions, including immune-mediated hemolytic anemia
(IMHA), immune-mediated polyarthropathy (IMPA),
and SLE. Anecdotally there are multiple reports of
successful management of dogs and cats with various
immune-mediated conditions with the use of a mul-
titude of immunomodulatory protocols and concur-
rent melatonin. However, I cannot recommend mel-
atonin as a single-agent therapy for these conditions.
Melatonin may promote glucocorticoid resistance.
Glucocorticoids are commonly used as first-line
therapeutic agents in patients with immune-medi-
ated conditions since this class of drug suppresses
peripheral T helper (Th) cell responses. Uniquely, T
Issue 05 | OCTOBER 2017 | 27