Mice given caffeine equivalent to a human drinking six to
eight cups of coffee a day were protected from developing experimental
autoimmune encephalomyelitis (EAE), the animal model for the human
disease Multiple Sclerosis (MS), according to researchers at Cornell
Caffeine is a well-known adenosine receptor blocker, and the
researchers believe results show the importance of this molecule in
permitting the infiltration of immune cells into the central nervous
system of patients with MS.
Dr. Jeffrey H. Mills, a postdoctoral associate in the laboratory of Dr.
Margaret S. Bynoe, presented the findings at Experimental Biology 2008
on April 7. The presentation was part of the scientific programs of the
American Society of Immunologists.
Multiple sclerosis is an autoimmune disease of the central nervous
system (CNS) that occurs when the body's immune system attacks and
damages nerves in the brain and spinal cord. The infiltration of immune
cells into brain and other CNS tissue is rarely seen in healthy
individuals without MS. What allows the immune cells to infiltrate the
CNS tissue of patients with MS is unknown. In earlier work, the Bynoe
laboratory became convinced that the molecule adenosine is responsible
for this infiltration.
Adenosine is widely present in the body and plays an important role in
many biochemical processes, such as energy transfer and the promotion
of sleep and suppression of arousal. The researchers' first studies
found that mice that lacked CD73, the enzyme necessary for synthesizing
extracellular adenosine, were protected from developing the mouse form
of MS (experimental autoimmune encephalomyelitis or EAE).
Additional studies involving immune cells from mice that lack CD73
further convinced them that normal CD73's ability to synthesize
extracellular adenosine was what was important for development and
progression of the MS-like disease. That helped explain the presence of
adenosine near the cells, but how did the compound get into the CNS
cells? Since adenosine must bind to its receptor in order to affect a
cell, the researchers reasoned that perhaps adenosine receptor
activation was what allowed for entry of immune cells into the brain
and spinal cord. To test that idea in the study presented at
Experimental Biology 2008, they turned to caffeine.
Caffeine's stimulatory effects on the CNS are in large part due to its
ability to bind to the same receptors as adenosine, thus blocking
adenosine's ability to affect CNS cells. Mice that consumed caffeine in
their drinking water were protected from development of EAE, the MS
model. Dr. Bynoe concludes that these experiments show that CD73 and
adenosine receptor signaling are required for the efficient entry of
immune cells into the CNS during the initiation and progression of EAE
in mice and, quite possibly, during the development of MS in humans.
Dr. Bynoe adds, "These results might mark the first in a series of
discoveries from our lab that could spawn the impetus for the
development of adenosine-based therapies for the treatment of MS."
Article adapted by Medical News Today from original press