Melatonin and the Immune System
jor at teleport.com
Sat Nov 18 21:02:18 EST 1995
Apart from melatonin's antioxidant prowess, another possible
explanation for melatonin's proven anti-aging properties in rodents is
its complex interaction with the immune system.
Melatonin's antioxidant properties were discovered in 1993. It's
possible role in the immune system was revealed about ten years earlier.
Georges Maestroni, director of the Center for Experimental Pathology
in Switzerland, has been the source of many of the significant findings.
Maestroni's first awareness that melatonin might play a role in
the immune system came in the early 1980s when he learned that animals that had
been deprived of their pineal glands -- the gland the produces melatonin --
had shrunken thymus glands. Thymus glands are key to the body's ability
to mount an effective immune response. If a lack of melatonin caused the
thymus to atrophy, then melatonin must be just as fundamental to immunity.
This idea has taken a while to take hold, partly because immunologists
have been slow to welcome hormones in general into the body's immune
response. Melatonin - an obscure hormone long thought to play no
significant role in human physiology - was an even less likely candidate.
Step-by-step, Maestroni and his colleagues, and most recently
immunologists in the United States, have begun to recognize melatonin's
central role in orchestrating the body's immune response.
One of melatonin's roles is to counteract the effect of stress on the
immune system, whether that stress is caused by viral infiltration,
emotional stress, drug-induced immunosuppression, or aging. For
exammple, animals studies have shown that melatonin is very effective in
reversing the effects of
psychic stress. In a key experiment, rodents were injected with a sub-lethal
dose of a virus.(EMCV virus) Half of the mice were then injected with
melatonin. Finally, both groups were subjected to restraint stress, a procedure
known to inhibit the immune response. At the end of 10 days, 82%
of the melatonin-treated rodents were still alive, compared to only 6 percent
of the controls. [Maestroni, Annals of the NY Academy of Sciences 1988; 521:
Melatonin has also been shown to reverse the decline in immunity
that accompanies aging. In a 1995 experiment, young and old mice were
injected with a virus that causes encephalitis, an often fatal brain
infection, Half of both groups were then treated with melatonin. In the
mice not given melatonin, not one of the old mice and only 6% of the young
mice survived. In the melatonin groups, 39% of the young group and a
surprising 56% of the old mice survived. In other words, melatonin had an
even greater protective effect on the immune system of the aged mice
than the young mice.
[Archives of Virology; 1995; 140:223-30.]
Melatonin has also reversed the immunsuppressive effect of
steroids on the immune system, as well as chemotherapy drugs. [Int.
J. of Neuroscience 1991; 61:289-98.]
Recent studies, most of them conducted in 1993, 1994, 1995,have
given new clues as to melatonin's specific mode of action. A recent
finding is that there is a melatonin receptor on a key immune cell called
the T-helper cell. ["T-Helper-2 lymphocytes as
peripheral target of melatonin signalling." J. of Pineal Research 1995;
18:84-89.] Once linked with the cell, melatonin increases production
of key cytokines (signalling cells)
Clinical trials involving melatonin are in the early stages.
However, so far, melatonin administration has enhanced production of
a number of important cytokines, including a 51% increase in IL-2, a 28% in
tumor necrosis factor alpha, and a 41 percent in interferon-gamma.
[Oncology Reports 1995; 2:45-7.]
Immune cells that have been enhanced by melatonin administration
include natural killer cells, T-helper cells, eosinophils, and null
cells. Salivary IgA, an important immunoglobulin, has also been enhanced
(IgA helps protect the mucous membranes from virus and infections.)
Another very promising use for melatonin is in protecting the bone
marrow from the toxic effects of chemotherapy, including cancer drugs and AIDS
drugs such as AZT. In both instances, melatonin has reduced toxicity to
the bone marrow without interfering with the positive effects of the
drugs. It is believed that melatonin accomplishes this feat by
marshaling more of a colony stimulating factor called GM-CSF. ["Melatonin
regulation of endogenous T-cell derived hematopoietic cytokines." Cancer
Reserach 1994; 54:2429-32.]
Melatonin's potential as an intervention in the aging process
are enormous. The hormone/antioxidant may be able to up-regulate
the immune system and counter the gradual decline in immunity that
occurs as we age. There are those who are now suggesting that the
gradual decline of melatonin production that accompanies aging may be
a significant factor in the atrophy of the
thymus, and the resulting impoverishment of the T-cell response. Melatonin
administration has successfully prevented the atropy of the thymus in
rodents. Will it do so in humans? TIme will tell.
When melatonin's antioxidant properties are added to its immuno-
enhancing properties, the net result is one of the most promising
anti-aging interventions yet discovered.
Coauthor, with Russel J. Reiter, Melatonin: Your Body's Natural WOnder Drug
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